A BS T R A C T Sheep red blood cells can surround, in vitro, some human peripheral blood lymphocytes in a formation called a rosette. The number of rosetteforming cells (RFC) in 50 normal persons had a wide range (4-40%). The organs of 13 human fetuses (11-19 wk conceptional age) were examined for the presence of RFC. The thymus possessed the highest percentage of RFC, the maximum being 65% of total thymocytes in two 1516 wk fetal specimens. Blood RFC were always present and their number slightly increased in the oldest fetuses. The bone-marrow showed 0-8% in the six fetuses studied. RFC were found in the spleen around the 13th wk and in the liver around the 17th wk of gestation. These observations lead to the hypothesis that human blood RFC may be chiefly thymic derived. Studies of patients with immunological disorders support this hypothesis: one patient with Nezelof syndrome had no blood RFC and four patients with Wiskott-Aldrich syndrome had a low number of blood RFC (1 and 1.5%). Patients with acquired hypogammaglobulinemia showed a normal percentage of RFC. With the fetal thymocytes, the percentage of inhibition with anti-i, serum increased with the fetal age to become complete in the oldest fetuses studied. Incubation of the oldest fetal thymocytes or the blood lymphocytes with anti-e serum or anti-ja serulmi completely inhibited the rosette formation. These results suggest that u-chain determinants are presenit on human fetal thymocytes and blood RFC. The significance of the presence of y-chain determinants on these cells is uniclear.

/pdf/the-human-rosette-forming-cell-as-a-marker-of-a-population-2utloos3tq.pdf

The Human Rosette-Forming Cell as a Marker of a Population of Thymus-Derived Cells

THERE is an obvious need for a marker that will differentiate one type of lymphocyte from another. The need has become urgent in view of recent evidence suggesting that there are at least two populations of lymphocytes, one thymus-derived and one bone marrow-derived, which participate in different ways in the immune response1. The theta (θ) isoantigen (θ is determined by a single locus with two alleles: θAKR found in AKR and RF mice and θC3H present in most other inbred strains of mice tested), described by Reif and Allen2,3, which is found chiefly in thymus lymphocytes and brain, and to a lesser extent in peripheral lymphocytes in mice, seemed a possible antigenic marker of thymus-derived lymphocytes. To establish that θ is such a marker, it is necessary to demonstrate that there is a discrete population of peripheral lymphocytes which carry the antigen and that these cells are thymus-dependent.

Theta isoantigen as a marker of thymus-derived lymphocytes in mice (Reprinted from Nature vol 224, pg 378-379, 1969)

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.

Membrane immunoglobulins and antigen receptors on B and T lymphocytes.

Fetal and early postnatal life represent critical periods in vertebrate immune system development. Disruption of such development by perinatal immunotoxic chemical exposure has been widely described in experimental animal models. The resultant inhibited postnatal immune responses in such animals are often more dramatic and persistent than those after exposure during adult life. Further, recent reports suggest that prenatal exposure to immunotoxicants may exacerbate postnatal aberrant immune responses (e.g., hypersensitivity disorders and autoimmune disease) in genetically predisposed rodents. Limited information is available regarding the possibility of inhibited postnatal immune capacity in humans as a result of developmental immunotoxicant exposure. The multifactorial nature of hypersensitivity and autoimmune responses will further complicate the elucidation of possible relationships between chemical exposure during ontogeny of the human immune system and immune-mediated disease later in life. Taken together, however, the available animal data suggest the potential for altered postnatal immune function in humans exposed to immunotoxicants (e.g., environmental chemicals and therapeutic agents) during fetal and/or early postnatal life.

Development of the murine and human immune system: differential effects of immunotoxicants depend on time of exposure

THE immune response to a specific antigen is characterized by the development of antibody-producing cells and of sensitized lymphocytes active in cell-mediated immunity. Although there is good evidence that antibody-producing cells are bone marrow-derived cells1–2, the role of thymus-derived cells is less well understood. Development of cell-mediated immunity is impaired in neonatally thymectomized animals3, and it is therefore likely that sensitized lymphocytes are thymus-derived cells. Spleen cell populations of mice immunized with allogeneic cells contain lymphocytes able to destroy in vitro appropriate target cells bearing the sensitizing alloantigens4–5. Earlier studies demonstrating the in vitro cytotoxic activity of sensitized thymus cells6 suggested that cytotoxic cells found in immune spleen cell populations were thymus-derived. As shown recently7–8 mouse thymus-derived cells in the peripheral lymphoid organs carry a surface marker, the θ alloantigen9, and are lysed when incubated in the presence of anti-θ serum and complement. This study was undertaken to test the effect of anti-θ serum on the cytotoxic activity of spleen cells sensitized to alloantigens. Its effect on alloantibody-producing cells present in the same spleen cell populations was tested in parallel.

Specific in vitro Cytotoxicity of Thymus-derived Lymphocytes sensitized to Alloantigens

MOUSE thymus cells possess a high concentration of the theta (θ)1 and Ly2 antigens Several approaches have demonstrated that the sensitivity of peripheral muriiie lymphocytes to the cytotoxic effect of θ and Ly antibodies is a thymus-dependent property The population of cells sensitive to the cytotoxic effect of θ antibodies disappears from lymph nodes3 and spleen4 after neonatal thymectomy Similarly, following neonatal thymectomy, the population of cells sensitive to Ly antibodies disappears from lymph nodes (unpublished results of M S and Yron) Following administration of heterologous anti-lymphocyte serum, a procedure resulting in elimination of thymus-dependent lymphocytes5,6, cells sensitive to θ antibodies disappear transiently from the lymph nodes7 and spleen4

Anti-theta antibodies for detecting thymus-dependent lymphocytes in the immune response of mice to SRBC.

A single injection of cortisol acetate into young mice induced a wasting syndrome similar to that observed in runt disease and in the post-thymectomy syndrome. The course of the disease was less severe if the dose of the drug was decreased or if the animals were older at the time of injection.

https://science.sciencemag.org/content/sci/143/3609/965.full.pdf

Wasting Disease Induced in Young Mice by Administration of Cortisol Acetate

Normal and isoimmune C3H and C57BL spleen cells were transferred intravenously into normal and irradiated allogeneic recipients and the fate of the donor cells determined by differential cytotoxicity and radioautographic techniques. It was found that spleen cells sensitized against their prospective recipients could be identified in the host's spleen for 1 day, whereas normal donor cells survived 2 to 3 days. Spleen cells presensitized with an indifferent antigen had survival times similar to normal donor cells. Irradiation of the recipients prior to cell transfer eliminated any difference in survival times between normal and presensitized donor cells in allogeneic hosts. It is concluded that the host plays an important role in the rapid destruction of spleen cells presensitized against host antigens.

Experiments in which sensitized and normal C57BL spleen cells were mixed and transferred into normal C3H mice indicated that as little as 5 to 10 per cent of the donor cell population need be sensitized for the entire mixture to behave as if it were obtained from a sensitized animal, as shown by its elimination in the 1-day interval.

/pdf/the-differing-survival-of-normal-and-sensitized-spleen-cells-1zqxg0gza5.pdf

Michael Schlesinger

Papers

Anti-theta antibodies for detecting thymus-dependent lymphocytes in the immune response of mice to SRBC.

Wasting Disease Induced in Young Mice by Administration of Cortisol Acetate

The differing survival of normal and sensitized spleen cells transferred to allogeneic hosts.