Charles E. Moody

Lymphocyte transformation induced by autologous cells. XV. Xenoantigens are not required for the proliferative response observed in the autologous mixed lymphocyte reaction

The autologous mixed lymphocyte reaction is the proliferative response of T cells cultured with autologous non-T cells. This reaction has been described as being immunological in nature, i.e., possessing memory and specificity. The generation of T cells with regulatory and effector function has also been reported during the course of this reaction. More recently it has been reported that the proliferative response observed is due to the exposure of T cells to xenoantigens used in separating T and non-T cells. We have found that the presence of antigens such as sheep erythrocytes and fetal calf serum is not required for the induction of proliferation in T cells by autologous non-T cells, although exposure to such antigens may augment [3H]thymidine incorporation. In certain individuals who are sensitized to these xenogeneic antigens, the proliferative response of their lymphocytes in the autologous mixed lymphocyte reaction is very greatly enhanced if exposed to xenoantigens.

Cell-type restriction in tolerance induced by hapten-modified cells.

Abstract Tolerance to the TNP haptenic determinant was induced by a single intravenous injection of trinitrophenylated syngeneic cells. Syngeneic spleen or thymus cells were capable of acting as carriers for tolerance induction while syngeneic bone marrow cells were not. Syngeneic spleen cells depleted of θ-positive and adherent cells were also suitable carriers for tolerance induction. Sonicated haptenated spleen cells, but not sonicated haptenated bone marrow cells induced tolerance. The ability of haptenated cells to induce tolerance was not correlated with their localization in lymphoid organs. Furthermore, cells recovered from the spleens of lethally irradiated animals reconstituted with bone marrow cells 1 week previously were incapable of inducing tolerance after hapten-modification. However, after 3 weeks, spleen cells from bone marrow-reconstituted mice had acquired the ability to induce tolerance. These results suggest that only certain types of syngeneic cells have the ability to act as carriers for tolerance induction; merely being syngeneic, and therefore presumably nonimmunogenic, is not sufficient to permit the cell to act as a carrier for tolerance induction.

The Influence of Sex Hormones on Immunological Processes in the Induction of Diabetes

Although diabetes mellitus in humans and experimental animals has been studied for many years, the basic mechanisms underlying the induction of diabetes are still not clear. Recent studies, including our own results, suggest that immune mechanisms may play important roles in the induction and pathogenesis of diabetes mellitus. The evidence supporting the idea of an immune mechanism for induction of diabetes includes the following observations: (1) the occurrence of lymphocyte infiltration of pancreatic islets in acute juvenile-onset- (Type I) diabetes (Gepts, 1965, 1972), (2) the occurrence of autoantibodies to islet cells in Type 1 (Bottazzo et al., 1974; MacCuish et al., 1974a,b), (3) the finding that diabetes mellitus could not be induced in athymic nude mice by diabetogenic M-strain encephalomyocarditis virus (EMC virus) (Buschard and Rygaard, 1976), or diabetogenic chemicals (Buschard and Rygaard, 1978; Paik et al., 1980), and (4) the finding that diabetes mellitus could be transferred to normal mice by the passive transfer of spleen cells from diabetic mice induced by streptozotocin (SZ) (Buschard and Rygaard, 1978; Kiesel et al., 1980).