Showing papers on "Cytotoxic T cell published in 1974"

Restriction of in vitro T cell-mediated cytotoxicity in lymphocytic choriomeningitis within a syngeneic or semiallogeneic system.

Abstract: RECENT experiments1–3 indicate that cooperation between thymus derived lymphocytes (T cells) and antibody-forming cell precursors (B cells) is restricted by the H-2 gene complex Helper activity in vivo operates only when T cells and B cells share at least one set of H-2 antigenic specificities Evidence is presented here that the interaction of cytotoxic T cells with other somatic cells budding4–5 lymphocytic choriomeningitis (LCM) virus is similarly restricted

Cell-Mediated Cytotoxicity, Allograft Rejection, and Tumor Immunity

Abstract: Publisher Summary The term “cell-mediated cytotoxicity” applies to lytic reactions that require the participation of lymphoid or non-lymphoid cells but not of added complement. It has been clearly established that several pathways, including different cell types, are involved in cytotoxic reactions in vitro. With membrane-associated antigens, such as transplantation, and tumor-associated antigens, the cytotoxic effect of effector cells on adequate target cells is most often highly specific and requires intimate contact rather than release of diffusible toxic factors. Specific cell-mediated cytotoxicity in vitro can be divided into three categories according to the nature of the effector cells.

Immunological surveillance against altered self components by sensitised T lymphocytes in lymphocytic choriomeningitis.

Abstract: THE cytotoxic activity1,2 of immune thymus-derived lymphocytes (T cells) for 51Cr-labelled fibroblasts, or macrophages infected with lymphocytic choriomeningitis (LCM) virus is restricted by the H-2 gene complex3,4. Specific lysis of LCM-infected monolayer cultures occurs only when targets and overlaying, sensitised T cells share at least one set of H-2 antigenic specificities.

Generation of cytotoxic t lymphocytes in vitro : i. response of normal and immune mouse spleen cells in mixed leukocyte cultures

Abstract: Mouse cytotoxic T lymphocytes (CTL) were generated in mixed leukocyte cultures (MLC) using spleen cells as responding cells and irradiated allogeneic spleen cells as stimulating cells. Cytotoxicity was assessed by a quantitative 51Cr assay system and the relative frequency of CTL in individual cell populations was estimated from dose-response curves. Inclusion of 2-mercaptoethanol in the MLC medium resulted in a 20–40-fold increase in the relative number of CTL generated at the peak of the response. Under these culture conditions, cell-mediated cytotoxic activity was detectable in MLC populations as early as 48 h after the onset of the cultures. When spleen cells from mice immunized with allogeneic tumor cells 2–4 mo previously were cultured with irradiated spleen cells of the same alloantigenic specificity (MLC-Imm), it was found that the cell-mediated cytotoxic response was detectable earlier and reached higher levels than that observed in a primary MLC. At the peak of the response, MLC-Imm populations were observed to lyse up to 50% of the target cells within 3 h at a lymphocyte: target cell ratio of 0.3:1. Immunological and physical characterization of the effector cells generated in MLC-Imm indicated that they were medium to large-sized T lymphocytes. Altogether, these studies suggested the existence of an anamnestic cell-mediated cytotoxic response in MLC-Imm.

Membrane immunoglobulins and antigen receptors on B and T lymphocytes.

Abstract: Publisher Summary This chapter describes membrane immunoglobulins and antigen receptors on B and T lymphocytes. There are several qualitative and quantitative distinctions between T-cell and B-cell M-Ig that may explain many of the apparent differences in reactivity of these cells without requiring the existence of a different set of V genes or non-Ig receptors in T cells. Both T and B cells derive from hematopoietic, precursor, stem cells by antigen-independent differentiation. This involves the activation of L-chain and p-type H-chain genes in both cell types. The T-cell and B-cell M-Ig differ primarily in density per cell and possibly in relative exposure on the cell surface with much of the H-chain Fc region inaccessible on T cells. Moreover, the antigen-recognition receptor of both T and B cells involves their M-Ig. On B cells, the receptor is solely the M-Ig, whereas on T cells it is suggested that the specificity of recognition controlled primarily by the M-Ig and binding of antigen to the cell can solely be by the M-Ig receptor. Finally, the activation of the T cell requires an additional interaction of the antigen with another ceIl surface structure that is coded for by a polymorphic H-2 linked gene.

Heterocytolysis by Macrophages Activated by Bacillus Calmette-Guerin: Lysosome Exocytosis into Tumor Cells

Abstract: The cytotoxic activity of activated macrophages against tumorigenic target cells appears to be mediated by lysosomal enzymes of activated macrophage origin. Lysosomes of activated macrophages are secreted directly into the cytoplasm of susceptible target cells, which subsequently undergo heterolysis. This reaction can be inhibited by agents which prevent the exocytosis of macrophage lysosomes (hydrocortisone) or which interfere with the action of lysosomal enzymes (trypan blue).

T-Cell Mediated Immunopathology in Viral Infections

Abstract: Virus-specific cytotoxic T cells are crucially involved in host recovery from primary infection Due to the immunological destruction of infected host cells, immunopathological damage may determine the severity of disease caused by poorly cytopathic or non-cytopathic viruses Some forms of virally induced hepatitis or of acquired immunodeficiency may be mediated by immunopathologically active virus-specific T cells

Evidence for the expression of Ia (H-2-associated) antigens on thymus-derived lymphocytes

Abstract: We have demonstrated in an anti-Ia serum the presence of specific antibodies reacting with T cells, as well as with B cells, using a highly sensitive dye exclusion test. This antiserum reacts with both spleen and lymph node in a characteristic biphasic titration curve killing up to 70% of these cells. It also reacts with cortisone-resistant thymocytes. The A.TH-α-A.TL serum can be absorbed with spleen, lymph node, cortisone-resistant thymus, or normal thymus cells. Further in vivo absorptions in BALB/c nude cannot remove all of the cytotoxic activity for normal BALB lymph node lymphocytes, while completely removing the activity for nude cells. A Thy-1 positive cell line derived from a C57Br leukemia is reactive with this anti-Ia serum.

Inhibition of pulmonary metastasis by intravenous injection of specifically activated macrophages

Abstract: Summary The ability of syngeneic macrophages from C57BL/6 mice bearing a progressively growing B16 melanoma to inhibit established pulmonary metastases in vivo was studied. Macrophages were cultured in vitro with supernatants obtained from cultures of B16 tumor cells alone or tumor cells and either normal, nonspecifically sensitized or specifically sensitized xenogeneic (rat) lymphocytes. The different groups of in vitro -treated macrophages were injected i.v. or i.p. into other C57BL/6 mice that had been given i.v. injections of 10,000 viable B16 melanoma cells 48 hr previously. The data demonstrated that specifically in vitro -treated macrophages injected i.v. but not i.p. into mice significantly reduced their number of established pulmonary metastases. Moreover, it appeared that the in vivo inhibition of tumor nodules was continuing at the time of sacrifice. These results support the experimental data that cytotoxic macrophages may occupy an important role in the defense against neoplasia. Furthermore, the application of xenogeneic activation of macrophages from tumor-bearing animals rendering them cytotoxic may provide a possible approach to therapy.

A one‐step procedure for separating mouse T and B lymphocytes

Abstract: A procedure is described for both depleting and obtaining in pure form Ig-bearing cells from mouse lymphoid populations. The Ig-bearing cells are identified by rosetting and the rosettes separated from the nonrosetting lymphocytes by centrifugation on Isopaque/Ficoll. The rosettes sink with the red cells and the nonrosetting lymphocytes float. The procedure is > 99.5 % efficient at depleting mouse lymphoid populations of Ig-rosetting cells and is also > 97 % efficient at removing the Ig-bearing cells detected by radioautography. Furthermore, after lysis of the red cells by hypotonic shock the Ig-bearing cells are recovered in a highly pure form. The total recovery of white cells and rosettes applied is > 85 %. This procedure was shown to produce a functional separation of T and B lymphocytes. The cell population depleted of Ig-rosettes behaved as a pure T cell preparation. It lacked precursors of antibody-forming cells, but contained virtually all of the Θ-positive lymphocytes, the bulk of the helper cells detected in two in vitro hapten carrier antibody responses and all the cells which responded and produced cytotoxic cells in MLC. In contrast, the preparation of Ig rosettes expressed B cell properties. This population contained all of the antibody forming cell precursors, few helper cells and Θ-positive lymphocytes and no MLC-responding cells. However, there was some evidence that a small subpopulation of T cells exists which possesses surface Ig. The separation system was used to formally demonstrate that carrier primed T cells collaborate with hapten primed B cells to generate an anti-hapten antibody response to a hapten-carrier conjugate. It was also established that in MLC responder B cells in no way collaborate with responder T cells to generate cytotoxic cells.

Tissue distribution of ia antigens: Ia on spermatozoa, macrophages, and epidermal cells

Abstract: Direct cytotoxic tests and absorption studies demonstrated thatI-region associated antigens (Ia) are not restricted to lymphocytes. Ia was found on spermatozoa, macrophages, and on epidermal cells, whereas Ia was absent from brain, liver, kidney, and fibroblasts. The possible biological meaning of these observations is discussed.

Cell surface markers for human T and B lymphocytes.

Abstract: A series of 4 cell surface marker systems have been developed and applied to human thymus, tonsil and purified blood lymphocyte populations. Double fluorochrome and mixed fluorochrome-rosette tests were used to determine cellular specificity and interrelationship of cells bearing the different markers and the results confirmed by a variety of cell separation procedures. Anti-brain antisera were, after appropriate absorption, T cell-specific and identified the same population as that forming rosettes with sheep erythrocytes. This T cell population was quite distinct from those cells, presumably B lymphcytes, with cell surface immunoglobulin readily demonstrable by fluorescence. A small proportion of “lymphoid” cells (“null” cells) lacked all three markers. Heat-aggregated human IgG (AggHIgG) was also used as a presumptive B cell marker and the results indicate that although most B lymphocytes do bind AggHIgG, presumably via an Fc receptor, a small proportion of thymocytes and presumptive T cells in tonsils also appear to possess a similar receptor. Almost all of these cells in tonsil were in fact lymphoblasts, thus raising the possibility that an Fc receptor is exposed or expressed on T lymphocytes when these cells are activated.

Generation of cytotoxic T lymphocytes in vitro. II. Effect of repeated exposure to alloantigens on the cytotoxic activity of long-term mixed leukocyte cultures.

Abstract: Mouse cytotoxic T lymphocytes (CTL) were generated in unidirectional mixed leukocyte cultures (MLC) using normal C57BL/6 spleen cells as responding cells and irradiated DBA/2 spleen cells as stimulating cells. Cytotoxicity was assayed on (51)Cr-labeled P-815 (DBA/2) target cells, and the relative frequency of CTL in individual cell populations was estimated from dose-response curves. Upon inclusion of 2-mercaptoethanol in the culture medium, it was found that significant CTL activity could be detected for as long as 3 wk in primary MLC. Reexposure of MLC cells to the original stimulating alloantigens after 14-41 days in culture resulted in significant cell proliferation and rapid regeneration of high levels of immunologically specific cytotoxicity. CTL activity in these secondary cultures increased dramatically within the first 24 h and reached higher peak levels than those found at the peak of the primary response. Furthermore, proliferation and reappearance of CTL activity could be demonstrated following each of as many as four sequential alloantigenic stimulations of the same initial cell population at 20-day intervals. Interestingly, cells recovered from MLC at the peak of the primary response on day 4 were insensitive to further allogeneic stimulation. Taken together, these results are consistent with the hypothesis that CTL differentiate in MLC to become long-lived memory cells which gradually lose their cytotoxic activity. Upon reexposure to specific alloantigen, such memory CTL rapidly regain their functional activity and proliferate to generate an expanded CTL population.

Cellular interactions in the proliferative response of human t and b lymphocytes to phytomitogens and allogeneic lymphocytes

Abstract: In vitro studies were performed to determine the proliferative responsiveness of human peripheral blood thymus-dependent (T) and thymus-independent (B) lymphocytes to phytomitogens and allogeneic lymphocytes. Recombination of T and B cells, with selective inhibition of proliferation of one of the two populations, was used to identify cellular interactions which may contribute to cell proliferation. The distinctive feature of human T lymphocytes to form rosettes with unsensitized sheep erythrocytes was utilized to separate human peripheral blood lymphocytes into highly purified resetting (T) and non-rosetting (B) cells. The proliferative response of these separated lymphocyte subpopulations to various stimulants was assessed from the uptake of tritiated thymidine into DNA. Phytohemagglutinin, concanavalin A, pokeweed mitogen, and allogeneic lymphocytes stimulated separated T cells, whereas no proliferation was observed with the T-cell-depleted B-cell population. This suggests that it is the human T cell which is activated directly by these stimulants. In the presence of T cells (proliferating or nonproliferating), B cells were capable of proliferation following stimulation with phytomitogens, but not in response to histocompatibility antigens. Thus, T-cell-mediated B-cell proliferation contributes to the overall lymphocyte response in phytomitogen-stimulated T + B cell mixtures, but not in human mixed leukocyte cultures. T-cell activation by allogeneic cells required the presence of monocytes; in contrast, the three tested phytomitogens stimulated T cells in the absence of monocytes. This indicates that direct interaction of mitogens with lymphocyte membrane receptors is sufficient to trigger T cells into proliferative response. However, monocytes considerably enhanced the proliferative response of T cells in a dose-dependent fashion; this monocyte-dependent mechanism of T-cell activation was predominant at lower concentrations of phytomitogens, and contributed relatively less at higher mitogen doses. Both, the direct, monocyte-independent, and the indirect, monocyte-dependent T-lymphocyte activation contribute to the total in vitro response of lymphocyte preparations to phytomitogens.

Escape from Immune Destruction by the Host through Shedding of Surface Antigens: Is This a Characteristic Shared by Malignant and Embryonic Cells?

Abstract: Summary The hypothesis is advanced that macromolecules normally found only in embryonic and fetal cells are also found in tumors because malignant cells, like the fetus, must develop mechanisms to avoid immunological destruction by the host. While anatomical factors play an important role in the “escape” of the fetus as well as the tumor, they are not by themselves adequate. In tumors, the shedding of antigens in a soluble form provides powerful protection because such antigens compete with the tumor for the effector processes of the immune response. Soluble antigens form adducts with antibodies as well as cytotoxic cells, which are then no longer capable of killing the tumor cells. Evidence is presented that the rate of spontaneous shedding of antigen may determine in part the growth pattern of the tumor in vivo. Sarcoma cells, which shed antigen rapidly, metastasize more readily than those with a slow spontaneous release of antigen. It is proposed that rapid shedding of transplantation antigens is a characteristic of embryonic cells and tumors.

Regulatory mechanisms in cell-mediated immune responses. I. Regulation of mixed lymphocyte reactions by alloantigen-activated thymus-derived lymphocytes.

Abstract: Regulatory effects of alloantigen-activated thymus-derived lymphocytes in mixed lymphocyte reactions have been demonstrated. Mice were injected into foot pads with allogeneic spleen cells; 4 days following sensitization spleen or regional lymph node cells from these animals were treated with mitomycin C and incorporated into MLR as regulator populations syngeneic to the responder cell type. Activated spleen cells suppressed MLR responses 60–90% whereas activated lymph node cells from the same animals enhanced MLR responses. Suppression by activated spleen cells was not due to cytotoxic effects nor to altered kinetics of the proliferative response. Studies of splenic suppressor cell generation in vivo revealed peak activity four days after alloantigen stimulation with no activity demonstrable at 7 days or at later times. Suppressor cell activity was abrogated by treatment with anti-θC3H serum and complement, and was not alloantigen specific.

T cell factor which can replace T cells in vivo.

Abstract: THE mechanism whereby thymus-derived (T) and bone marrow or bursa-derived (B) lymphocytes cooperate in the induction of an antibody response is of great importance in immunology. It has been suggested that T cells concentrate antigen by their surface receptors to present a multideterminant antigen array directly to B cells1,2; or that T cells secrete a special class of cooperating antibody (IgX) for this purpose, which could specifically present antigen at the surface of a third cell, the macrophage3,4; or that the product of recognition of antigen by T cells has some non-specific mitogenic or stimulatory effect on B cells5,6. Recent work with in vitro systems has indicated that various factors produced by T cells, either after contact with a specific antigen or following stimulation by allogeneic cells, can replace the requirement for T cells in antibody formation7–14.

Enhancing T lymphocytes from tumor‐bearing mice suppress host resistance to a syngeneic tumor

Abstract: The cell-mediated immune response of animals to a lethal syngeneic tumor was investigated by inoculating C57BL mice with Lewis lung carcinoma (3LL) cells T lymphocytes, obtained from the enlarged spleens of the tumor-bearing mice were found to be cytotoxic to 3LL target cells in vitro. However, we found that such spleen cells enhanced tumor growth in vivo when mice were injected with a mixture of spleen cells and tumor cells. Removal of T lymphocytes by treatment of the spleen cells with anti-Θ serum plus complement reduced the enhancement of tumor growth. Hence, the tumor enhancing cells, like the cytotoxic cells, appeared to be T lymphocytes. Removal of T lymphocytes from normal mice by adult thymectomy before tumor inoculation led to a reduction in the number of tumor metastases. Thus, enhancing T lymphocytes appear to exist in normal as well as in tumor-bearing mice. Investigation of this mechanism of tumor enhancement suggested that the enhancing T lymphocytes act as suppressor T cells inhibiting natural immune resistance to tumor growth.

Immunologic Functions of Isolated Human Lymphocyte Subpopulations II. Antigen Triggering of T and B Cells in Vitro

Abstract: Soluble and cell surface antigen-induced triggering of highly purified human T and B cells was studied measuring 3 H-thymidine incorporation in vitro. T cells but not B cells from antigen-sensitive donors responded to specific soluble antigen challenge. Nonsensitized cells failed to respond. The addition of sensitized T cells to autologous B cells did not induce B cells to proliferate in response to soluble antigen. In one-way mixed leukocyte cultures, T cells but not B cells incorporated 3 H-thymidine in response in allogeneic mitomycin-treated targets. In contrast, both T and B target cells were capable of inducing proliferation of allogeneic T cells.

Cell-mediated immune responses in vitro : i. suppression of the generation of cytotoxic lymphocytes by concanavalin a and concanavalin a-activated spleen cells

Abstract: The effects of soluble concanavalin A (Con A) or Con A-activated spleen cells on the generation of cytotoxic lymphocytes (CL) in mixed leukocyte cultures (MLC) were examined. Mitogenic concentrations of soluble Con A or small numbers of Con A-activated spleen cells substantially inhibited CL responses. The suppression was partial rather than absolute and was critically dependent upon the concentration and time of addition of soluble Con A or Con A-activated spleen cells to the MLC. Suppressive effects of Con-A activated spleen cells were mediated by T cells since suppressor cell activity was abrogated by treatment of spleen cells with anti-theta serum and complement before or after Con A activation. X irradiation of spleen cells before Con A treatment also abrogated generation of suppressor cell activity. After activation by Con A, however, the function of suppressor cells was radioresistant. Although the precise mechanism(s) of suppression is, as yet, unknown, the precursors of CL must be exposed to Con A-activated cells during the early phases of the immune response for suppression to occur. Kinetic studies revealed that suppression of CL responses was not due to a failure to initiate an immune response, but represented a response which developed initially, but subsequently aborted. The relevance of these observations to the concepts of T-cell-T-cell interaction and regulatory control of immune responses by T cells is discussed.

Cytotoxity of non-T versus T-lymphocytes from melanoma patients and healthy donors on short- and long-term cultured melanoma cells,.

Abstract: Lymphocytes from 25 healthy donors were separated into T- and non-T-fractions by means of E and EAC rosette-formation. The unfractionated lymphocyte population was tested simultaneously with E and non-EAC rosette-forming cells (T-cells) and EAC and non-E rosette-forming cells (non-T cells) on melanoma cells from cell lines and short-term cultures. More frequent and stronger cytotoxic effects were seen on melanoma target cells from cell lines than from short-term cultures. The cytotoxic effects of the unfractionated lymphocyte populations were always recovered in the non-T-cell populations. Occasionally also T-cell cytotoxicity was seen on melanoma cells from cell lutes. Compared to the T-cell effects, the non-T cells always showed stronger cytotoxic effects. Lymphocytes from selected melanoma patients (patients with known cytotoxic lymphocytes) were also tested tegether with lymphocytes from healthy donors. The cytotoxic effects scored with the unfractionated melanoma patients' lymphocytes, which in general were stronger than the effects seen with the corresponding lymphocyte populations from healthy donors, again appeared to be located mainly in the non-T-cell populations.

Cross-reacting tumor-associated antigen (s) among chemically induced rat colon carcinomas.

Abstract: Summary Cross-reacting tumor-specific surface antigens were demonstrated by in vitro microcytotoxicity assays among colon carcinomas induced by three separate chemical carcinogens in two different rat strains. Lymphocytes from rats bearing primary or isografted colon carcinomas or from rats immunized with cultured colon tumor cells were consistently cytotoxic to multiple colon tumor target cells. The colon carcinomas were induced by three different chemical carcinogens. Tested lymphocytes were not cytotoxic to normal kidney, normal colon mucosa, or polyoma tumor target cells. Furthermore, no cross-reactivity could be detected between two colon carcinomas and either a mammary carcinoma or a fibroadenoma. Sera from three rats bearing primary colon tumors induced by two different chemical carcinogens blocked the lymphocyte-mediated cytotoxicity of all the primary colon effector cell-colon tumor target cell pairs tested. Sera from animals bearing a polyoma virus-induced sarcoma did not inhibit the cell-mediated immunity in the colon tumor system. Sera from rats bearing the primary colon carcinomas did not suppress the cytotoxicity of lymphocytes from polyoma tumor-bearing rats against polyoma tumor target cells. It is postulated that the chemically induced rat colon carcinomas tested share common tumor-specific surface antigen(s).

Cholinergic Augmentation of Lymphocyte-Mediated Cytotoxicity. A Study of the Cholinergic Receptor of Cytotoxic T Lymphocytes

Abstract: Cholinergic agonists have previously been shown to augment the ability of sensitized lymphocytes to injure cells bearing the sensitizing alleantigens. The cholinergic receptor of the attacking lymphocyte population has been studied with pharmacological manipulation of an in vitro system that quantitates the injury mediated by sensitized attacking cells upon target cells. The data reveal that muscarinic ligands are several orders of magnitude more potent than nicotinic agents in altering cytotoxicity.

Cellular Immunoadsorbents: a Simplified Technique for Separation of Lymphoid Cell Populations

Abstract: A simplified and efficient technique for separating T lymphoid cells from non-T cells of mouse, rat and man has been developed. The fractionation procedure is based on the capacity of non-T lymphoid cells to bind antigen-antibody complexes through an Fc receptor. Lymphoid cells are adsorbed on antibody-coated sheep erythrocyte (EA) monolayers prepared in polystyrene Petri dishes previously treated with poly-l-lysine. Adsorption of spleen cells on these monolayers, assisted by a 5-min centrifugation, resulted in 90 to 98% depletion of the Fc receptor-bearing cells (mostly B lymphocytes, but also macrophages and polymorphonuclear leukocytes) in the non-adherent cell population. Eighty to 90% of the adherent cells were capable of forming EA rosettes and could be recovered after lysis of the erythrocytes. The non-adherent fraction comprised at least 90% T-cells. This was determined for mouse and rat spleen cells by lysis with anti-thymocyte serum and complement, and by the absence of immunoglobulin-bearing cells. The specificity of the adsorption was further substantiated by the following observations: 1) lymphoid cells lacking an Fc receptor were not adsorbed; 2) the adsorption to EA monolayers was inhibited by antigen-antibody complexes or by aggregated γ-globulin; and 3) only 10 to 15% of the Fc receptor-bearing cells were attached to non-sensitized erythrocyte (E) monolayers. Fractionation of spleen cells obtained from rats immunized against a syngeneic tumor yielded two separate fractions of cytotoxic lymphoid cells: one (non-adherent, T cells) mediating direct target cell destruction, and the other (adherent, non-T cells) mediating lysis of antibody-coated target cells.

Cell‐mediated cytotoxicity against ectromelia virus‐infected target cells. I. Specificity and kinetics

Abstract: Spleen cells from mice immunized intravenously with attenuated ectromelia virus were cytotoxic for target cells infected with virulent ectromelia virus in the absence of exogenous complement; cytotoxicity was measured by 51Cr release from target cells. L929 cells were the most sensitive target cells, but the effect could also be demonstrated with P-815 mastocytoma cells and chick embryo cells; mouse embryo cells were unsatisfactory. Hyperimmune anti-ectromelia serum and complement was not significantly cytotoxic although fluorescein-conjugated antiserum stained virus-infected L929 cells. Release of 51Cr label from ectromelia-immune spleen cells (at a spleen cell: target cell ratio of 100: 1) increased in a linear manner with time, until a plateau was reached at 20–24 hours. Cytotoxicity appeared to be specific in that ectromelia-immune spleen cells killed ectromelia-infected L929 cells, but not uninfected L929 cells, whereas spleen cells from mice immunized with Listeria monocytogenes (a potent stimulus for cell-mediated immunity) or from normal mice, did not kill ectromelia-infected L929 cells. Spleen cells from mice immunized with vaccinia virus (a poxvirus closely related to ectromelia) were cytotoxic for ectromelia-infected L929 cells. Spleen cells from mice immunized with ectromelia virus had acquired cytotoxic activity by 2 days after immunization. Cytotoxic potency reached a peak at 6 days and had declined to a low level by day 10. The potential significance of the phenomenon in relation to control of viral infection is discussed.

Lymphocyte subpopulations in the blood of newborn infants

Abstract: Assays of lymphocyte subpopulations and function have been applied to cells from the cord blood of twenty-four infants The results are compared with those obtained in healthy adults T cells, assayed by spontaneous rosette formation with sheep red blood cells (E rosettes) were present in lower proportion in cord (53%) than in adult blood (65%) There was a higher proportion of lymphocytes bearing stainable immunoglobulin in cord (32%) than in adult blood (22%) From the blood lymphocyte counts it was calculated that both T and B lymphocytes are present in greater numbers in the newborn infants' blood than in adults Comparison of DNA synthesis showed that cord blood leucocytes had a higher spontaneous rate, but there were only minor differences in the lymphocyte mitotic response to phytohaemagglutinin (PHA) The response of cord blood lymphocytes was slightly lower to a submaximal stimulus and higher to a maximal stimulus There was a correlation between the submaximal response and the proportion of E rosetting cells The most striking differences between infant and adult blood lymphocytes were in their cytotoxic activity against homologous target cells (Chang cells) Antibody-dependent cytotoxicity (K-cell activity) was readily detected using cord blood leucocytes, though it was lower than that of adult cells PHA-induced cytotoxicity was very low in all cord blood samples, and in many cases was almost unmeasurable This dissociation between the two types of cytotoxic activity is consistent with other evidence that they may be mediated by different cell types The assays were also applied to blood samples taken from five mothers of tested infants immediately after delivery While some differences from normal adults were found with the mothers' lymphocytes they did not mirror those of the cord blood samples This suggests that the pattern found for cord blood lymphocytes is not due to maternal factors crossing the placenta