Showing papers in "Transplantation in 1970"
TL;DR: The test possesses sufficient sensitivity to detect tumor-specific as well as histocompatibility antigens and reduction of target cell survival was also observed with cells from mice receiving either single or multiple immunizations.
Abstract: SUMMARYA method for assaying cell-mediated cytotoxicity against cultured target cells in 10 µl of medium is described The test possesses sufficient sensitivity to detect tumor-specific as well as histocompatibility antigens Lymphoid cells from the peritoneal cavity, spleen, and peripheral blood ex
458 citations
TL;DR: The results show that stable long-term chimerism can be achieved in mismatched recipient dogs when intensive methotrexate is begun immediately after marrow transplantation and continued for a prolonged period of time.
Abstract: SUMMARYImmunosuppressive therapy with high doses of methotrexate beginning 1 day after allogeneic bone marrow transplantation was evaluated for its effectiveness in preventing or delaying the lethal graftversus-host disease in dogs. A short-term regimen of methotrexate for 6 days after transplantati
292 citations
TL;DR: Graft-versus-host activity can be assayed in both Ag-B-disparate and Ag- B-identical strain combinations although, in the latter case, about 100 times as many cells are required to produce the same amount of lymph node enlargement.
Abstract: SUMMARY When parental strain spleen cells or thoracic duct lymphocytes were injected into the feet of F1 hybrid recipients, the draining popliteal lymph nodes reached a weight which was up to 30 times greater than that of control lymph nodes. Seven days after injection, the mean lymph node weight was linearly related to the dose of cells injected on a double log scale. As a graft-versus-host assay, this method was found to be more sensitive as well as more convenient than other methods which have been used in the rat. The degree of lymph node enlargement produced by a given dose of cells was influenced by the volume in which they were injected, the precise site of injection, and the age of the recipient. On the other hand, the sex of the recipient and addition of F1 hybrid cells to the inoculum did not affect the lymph node weight. Graft-versus-host activity can be assayed in both Ag-B-disparate and Ag-B-identical strain combinations although, in the latter case, about 100 times as many cells are required to produce the same amount of lymph node enlargement.
282 citations
231 citations
226 citations
TL;DR: In this paper, a method was developed by which a set of dog kidneys could be shipped in a small box containing ordinary ice for periods of up to 30 hours with almost no detectable damage.
Abstract: A method was developed by which Summary
kidneys could be shipped in a small box containing ordinary ice for periods of up to 30 hours with almost no detectable damage. A total of 54 dog kidneys were stored in saline at 0°C with ice slush for 16, 24, and 30 hours, using surface cooling alone or combined with initial perfusion with several solutions. To evaluate the efficacy of storage, the contralateral kidney was removed at the time of reimplantation of the stored kidney and blood levels of creatinine and urea were followed daily. The final relatively simple scheme (infusion of mannitol, phenoxybenzamine, and a special perfusate) resulted in uniformly good preservation in all 7 kidneys stored for 24 hours and all 3 kidneys stored for 30 hours (there was one technical failure). Other perfusates, such as Ringer's lactate and 10% invert-sugar solutions, gave inferior results. The new perfusate extended the time of simple ice storage from 12 hours to 30 hours.
198 citations
163 citations
TL;DR: It is postulated that antibodies produced by the mother against incompatible HL-A antigens of the fetus may have a deleterious effect upon the fetus in subsequent pregnancies.
Abstract: A large proportion of the sera from 574 parous women was shown to contain cytotoxic antibodies against HL-A tissue antigens. After their second pregnancies, one-quarter of the women had cytotoxins, and after the sixth, one-half of the women had these antibodies. Retrospective studies of the outcome of pregnancies showed that women with antibodies had a significantly higher incidence of infants with congenital anomalies than did those without antibodies. It is postulated that antibodies produced by the mother against incompatible HL-A antigens of the fetus may have a deleterious effect upon the fetus in subsequent pregnancies.
127 citations
TL;DR: Evidence of a lymphocyte antigen system behaving as a histocompatibility system was brought out by a significant lengthening of the survival of skin grafts in the case of compatible siblings.
Abstract: SUMMARY Lymphocytotoxic isoantibodies were developed in swine by skin grafts. Seventy swine distributed into several families were tested by the sera. In each family, the parents' characters determined by these sera were transmitted to the piglets according to Mendelian laws.Evidence of a lymphocyte antigen system behaving as a histocompatibility system was brought out by a significant lengthening of the survival of skin grafts in the case of compatible siblings.
95 citations
78 citations
TL;DR: Spleen was shown to be the richest in this antigen, followed in order by lung, liver, intestine, kidney, and heart, while aorta is rather poor while fat and brain contain practically none.
Abstract: SUMMARY A monospecific serum which recognizes antigen HL-A2 (Mac) of the HL-A system was systematically absorbed with homogenates of fresh organs of three individuals possessing this antigen. Spleen was shown to be the richest in this antigen, followed in order by lung, liver, intestine, kidney, and heart. Aorta is rather poor while fat and brain contain practically none.
TL;DR: Human fetal cells grown in tissue culture monolayers were tested using the technique of mixed agglutination and were found to possess some of the antigens controlled by the HL-A locus, indicating that spermatozoa, like the trophoblastic syncytia, either do not express their transplantation antigen or are lacking in these specificities.
Abstract: SUMMARYHuman fetal cells grown in tissue culture monolayers were tested using the technique of mixed agglutination and were found to possess some of the antigens controlled by the HL-A locus. Gestational specimens ranging from 6 weeks through maturity were studied. All fetal homogenates, as well as
TL;DR: The hypothesis is advanced that the cells responsible for cytotoxicity in spleens at 7 days after immunisation are immunoblasts (i.e., large pyroninophilic cells), as had earlier been shown to be the case for cells in the lymph from immunised donors.
Abstract: Summary: Spleen cells from C57BL mice immunised once with L5178Y lymphoma cells, which are of DBA/2 genotype, were assayed for cytotoxicity by measuring their effect on the growth of L5178Y cells in vitro. Two populations of cytotoxic spleen cells were distinguished: (1) those found predominantly 6-12 days following immunisation; and (2) those found 14 days and later following immunisation. The cytotoxic activity of the “early” cells was relatively radioresistant and was not affected by drugs which inhibit nucleic acid synthesis. These early cells resemble those found in lymph from draining nodes, which are cytotoxic only 4-8 days after immunisation. Spleen cells taken from mice and rats 21 days after immunisation lost cytotoxic activity by exposure to 500 R of X-rays and to Mitomycin C, actinomycin D, and potassium cyanide. Removal of macrophages did not reduce the cytotoxicity of either class of spleen cell. Cytotoxicity was unaffected by the addition of a source of complement, but this does not exclude the participation of some complement components (which are synthesised by spleen cells). By following the release of 61Cr, it was shown that the L5178Y cells lysed sooner after the addition of spleen cells taken at 7 days, as compared to 21 days, after immunisation. The 21-day spleen cells acquired some of the properties of 7-day spleen cells (such as radioresistance) after exposure to target cells for 10 hr. The hypothesis is advanced that the cells responsible for cytotoxicity in spleens at 7 days after immunisation are immunoblasts (i.e., large pyroninophilic cells), as had earlier been shown to be the case for cells in the lymph from immunised donors. These cells, it is postulated, are directly cytotoxic, possibly because they already possess the machinery for the synthesis of antibody. The cells found in spleen 21 days after immunisation are only potentially cytotoxic and become transformed—hence their radiosensitivity—by contact with target cell antigen into the actual cytotoxic cells, which are presumably immunoblasts
TL;DR: “Allogeneic inhibition” did not occur in any of these animals despite the presence of diverse H-2 antigenic cell types, and the morphogenesis of mosaic hairs was strikingly modified when one of the two clonal components was eliminated.
Abstract: Histocompatibility antigens have been detected on melanoblasts and hair follicle cells by means of test grafting of skin from allophenic mice containing two homozygous subpopulations of cells with different alleles at the H-2 locus. Melanoblasts bore a visible color marker (e.g., B/B ↩ b/b) and hair follicle cells were marked at the agouti locus (A/A ↩ a/a). In skin grafts to parental isogenic strains, there was selective survival of those melanoblasts and hair follicle cells whose visible phenotypes were from the same H-2 strain as was the host, while cells of the foreign H-2 strain were destroyed. Genotype-specific homograft rejection by the hosts was highly localized to the homologous cells, even when the genotypic cell strains were admixed within a single hair bulb. Donor grafts had some individual hairs with both black and brown pigment granules attributable to B/B and b/b cells, respectively, or intermediate degrees of agouti banding attributable to presence of both A/A and a/a cells; only one pure strain contributed to such follicles after rejection of incompatible cells. The morphogenesis of mosaic hairs was strikingly modified when one of the two clonal components was eliminated. Hair follicle H-2 antigens in the in situ skin also sometimes differed from H-2 antigens of the contained melanoblasts, e.g., when C57BL/6 pigment cells entered a BALB/c hair and there produced pheomelanin. “Allogeneic inhibition” did not occur in any of these animals despite the presence of diverse H-2 antigenic cell types.
TL;DR: This finding shows that immunologically competent cells acquire specific cytotoxicity toward H-2-incompatible target cells carrying the stimulating antigen under the conditions of the mixed culture.
Abstract: SUMMARY C57BL spleen or lymph node cells cultured for 4 days with mitomycin- treated CBA or A. CA spleen cells were tested in vitro for cytotoxicity against CBA and A.CA fibroblastic target cells. It was found that the cytotoxicity of C57BL spleen or lymph node cells toward target cells of the same genotype as those to which they had been preexposed in such a mixed leukocyte culture was greater than the cytotoxicity toward the other target cell used. This finding shows that immunologically competent cells acquire specific cytotoxicity toward H-2-incompatible target cells carrying the stimulating antigen under the conditions of the mixed culture.
TL;DR: The number of men who have become fathers was obtained and both groups were contrasted with groups of patients on maintenance haemodialysis to assess the relationship of pregnancy to renal graft function.
Abstract: SUMMARYIsolated cases of pregnancy after renal transplantation have been reported. This survey attempted to collect all of the cases known at present and to assess the relationship of pregnancy to renal graft function. Similarly, the number of men who have become fathers was obtained for comparison
TL;DR: It is suggested that a general inhibition of expression of immunity develops as a consequence of the immune reaction, possibly mediated by humoral factors.
Abstract: The survival times of H-2 incompatible skin allografts were studied in F1 hybrids treated with parental strain lymphoid cells. The injection of 50×106 A/Sn lymphoid cells into A/Sn×CBA F1 hybrids greatly prolonged the survival of 5M skin allografts applied 7 days later. Suppression of allograft rejection was observed also in F1 recipients that were actively or adoptively immunized against the skin graft donor.
The immunocompetence of the sensitized F1 hosts was supressed to a greater degree than that of normal non-sensitized recipients. It is unlikely that immuno-incompetence is caused by basic effects of the graft-versus-host reaction or by antigenic competition since overt signs of a graft-versus-host reaction were not a necessary prerequisite for immunosuppression. It is suggested that a general inhibition of expression of immunity develops as a consequence of the immune reaction, possibly mediated by humoral factors.
TL;DR: Antibodies which kill lymphocytes from other persons were found in 35 of 113 healthy subjects immunized with influenza, polio, and other vaccines, suggesting that a wide scale cross reactivity of microbial and human lymphocyte antigens may exist.
Abstract: SUMMARY Antibodies which kill lymphocytes from other persons were found in 35 of 113 healthy subjects immunized with influenza, polio, and other vaccines. These lymphocytotoxic antibodies were characteristically more active at colder temperatures (15 C) and were IgM in nature, as were similar cytotoxins found earlier in systemic lupus, rheumatoid arthritis, infectious mononucleosis, rubella, and measles. It is suggested that a wide scale cross reactivity of microbial and human lymphocyte antigens may exist.
TL;DR: It is suggested that the in vitro graft reaction system is based on an interaction between lymphoid cells, in which thymus cells act as antigen-recognizing cells, and that thymUS cells may participate in or fulfill the role of memory cells.
Abstract: SUMMARY The activity of rat lymphocytes from different organs was compared in an in vitro system based on sensitizing rat lymphocytes on C3H mouse fibroblast monolayers and then testing the lytic effect of transformed lymphocytes (large pyroninophilic cells) against the C3H cells. Thymic cells were found to manifest very low lytic activity, spleen cells were significantly more active than thymus cells, and lymph node cells had the highest activity. These differences could not be attributed to differences in the extent of transformation, since thymus cells sensitized on C3H fibroblasts produced at least as many large pyroninophilic cells as did lymph node cells. We assumed that rat thymus cells which can respond by transformation to mouse monolayers may play a role in determining the lytic process of other lymphocytes. To test this hypothesis, thymus cells were added to spleen cells and the admixed cell population did indeed show an increased lytic effect, compared to thymus or spleen cells alone. Rat thymus cells, presensitized against C3H mouse fibroblasts (8-13 days in culture), were mixed with fresh spleen cells and the mixture was tested for lysis on C3H monolayers. An enhanced lytic activity was manifested, appearing earlier than when any other lymphoid cell combinations were tested in an identical manner. The antigenic specificity of this system was directed by the presensitized thymus cells, which were found to be capable of interacting effectively with nonsensitized spleen cells, even when cultured on syngeneic cells after sensitization and before being mixed with the spleen cells. We suggest that the in vitro graft reaction system is based on an interaction between lymphoid cells, in which thymus cells act as antigen-recognizing cells, and that thymus cells may participate in or fulfill the role of memory cells.
TL;DR: Eleven pairs of dogs exchanged at least three skin grafts within the pairs until a “white graft” occurred and serum lymphocytotoxic antibody was demonstrated and irreversible hyperacute rejection had already begun.
Abstract: SUMMARY Eleven pairs of dogs exchanged at least three skin grafts within the pairs until a “white graft” occurred and serum lymphocytotoxic antibody was demonstrated. Kidneys were then exchanged within the pairs. Six of eight kidneys in untreated dogs rejected by 12 hr, two within 36 hr. Four azathioprine-treated dogs rejected at 2, 4, 12, and 44 hr. Four dogs treated with heparin before and after transplantation did not reject hyperacutely. One animal received heparin at 15 min posttransplantation, but irreversible hyperacute rejection had already begun. Five aspirin-treated recipients did not reject acutely but were oliguric. Control grafts showed red cell aggregates in dilated peritubular and glomerular capillaries as early as 5 min. Fibrin-platelet microthrombi, swollen and vacuolated endothelial cells, and damage to arterial media were also early findings. By 24 hr, vascular thrombosis and cortical necrosis were evident. Aspirin-treated dogs showed similar but less severe changes. Heparin-treated dogs had only occasional intravascular red cell microaggregates but, by 4 days, cellular rejection was evident.
TL;DR: Statistical analysis of the survival data demonstrated the superiority of the methotrexate regimen as well as the effectiveness of the cyclophosphamide regimen.
Abstract: SUMMARYThe effectiveness of immunosuppressive therapy with methotrexate was compared to that with cyclophosphamide in preventing or delaying the lethal graft-versus-host disease in dogs following bone marrow transplantation from unrelated donors that were mismatched with their recipients by canine h
TL;DR: Identification and measurement of the antigen-induced donor cell reaction permits one to distinguish between the GVHR proper and its effect on the host and thereby allows one to relate GV HR to other forms of antigen- induced lymphoid cell proliferation.
Abstract: SUMMARY The natural course of development of local renal graft-versus-host reactions (GVHR) was investigated in several donor-host combinations. In each case, the pathogenesis of the local invasive-destructive reaction was associated with the proliferation of donor cells. This proliferative activity was antigen-dependent, for it did not occur when specifically tolerant donors were used, and it was largely confined to the local lesion itself. The growth of this dividing donor cell population, measured by incorporation of 125I-labeled 5-iodo-2'-deoxyuridine into deoxyribonucleic acid, was approximately exponential during the invasive-destructive phase of the local GVHR. When donor and host differed at the Ag-B locus, the rate of development of the local lesion was not appreciably altered by prior sensitization of the donor and still waited upon the development of a proliferative response. Immunological memory was demonstrable only when donor and host were compatible at the Ag-B locus, in which case prior sensitization was required to obtain a reaction. The competence of donor spleen cells to initiate a local GVHR across an Ag-B barrier develops during the 3rd week of life, whether or not the donors are derived from axenic stock. The reaction of the donor cells in the inoculated kidney was shown to induce a proliferative response on the part of host cells in the spleen. The intensity and duration of the splenic response were variable and poorly correlated with the intensity of the renal reaction which evoked the response. The familiar stigmata which are generally associated with systemic GVHR were seen in a minority of hosts with well developed renal reactions. Identification and measurement of the antigen-induced donor cell reaction permits one to distinguish between the GVHR proper and its effect on the host and thereby allows one to relate GVHR to other forms of antigen-induced lymphoid cell proliferation.
TL;DR: The result of the graft-versus-host reaction caused by parental immunocompetent cells affects the differentiation of parental colony-forming cells.
Abstract: SUMMARY A histological study was carried out on the spleen and bone marrow colonies of (DS X C57BL) F1 hybrid mice. Parental (DS) lymph node cells injected into F1 hybrid mice after sublethal irradiation eradicated the endogenous colonies of the host. The host colonies disappeared earlier in the spleen than in bone marrow. When parental spleen or bone marow cells were added to the lymph node cells, colonies appeared in the spleens of F1 hybrid mice whose endogenous colonies were eradicated by parental lymph node cells. The fact that the number of colonies was directly proportional to the number of added spleen cells suggested the parental origin of these colonies. In this case, myeloid colonies outnumbered erythroid colonies (erythroid to myeloid colony ratio of below 0.5). The differentiation pattern was different from those of endogenous colonies, exogenous colonies coming from spleen cells of hybrid donors and exogenous colonies which appeared in F1 hybrid mice injected with parental bone marrow cells only (erythroid to myeloid colony ratio of above 2.5). The result of the graft-versus-host reaction caused by parental immunocompetent cells affects the differentiation of parental colony-forming cells.
TL;DR: H-2 alleles of translocation stocks T138 and T190 were analyzed in the direct hemagglutination test and by in vivo absorption with oligospecific antisera and it is hypothesized that H-2m allele of strain AKR.M might have also arisen by crossing over between alleles H- 2k of strainAKR.
Abstract: H-2 alleles of translocation stocks T138 and T190 were analyzed in the direct hemagglutination test and by in vivo absorption with oligospecific antisera. The alleles of both stocks were found to be indistinguishable from the H-2q allele of strain DBA/1. This conclusion was confirmed by an F1 test with skin grafts. The possible origin of the H-2q allele of the translocation stocks and its possible relationship to H-2q alleles of other strains are discussed. An H-2 recombinant which arose by crossing over between H-2a of B10.A and H-2q of T138 was also analyzed. The recombinant has a new combination of H-2 antigens which we propose to call H-2y. The H-2y allele has its D end derived from H-2a and its K end derived from H-2q. Factors controlling antigens H-2.17 and H-2.30 are placed by this recombinant in the opposite sides from Slp in the H-2 map. On the basis of these and other data, it is hypothesized that H-2m allele of strain AKR.M might have also arisen by crossing over between alleles H-2k of strain AKR. and H-2q of noninbred strain M.