Patterns of Immune Reactivity in Autoimmune Murine Strains

Abstract

Abstract We compared spleen cells from immunologically normal mice to those from five autoimmune murine strains (NZB, NZB × W, BXSB, MRL/l, MRL/n) in the cell-mediated lympholytic response in vitro to spleen cells from syngeneic, allogeneic but H-2 identical and H-2 incompatible mice. NZB spleen cells sensitized with irradiated allogeneic but H-2d identical spleen cells lysed unmodified H-2 identical cells in a strong, cross-reactive, unidirectional response, and lysed similarly, but to a lesser extent, syngeneic cells. The NZB anti-H-2d activity was mediated by T cells and was directed against both T and B target cells. Although the anti-H-2d activity is known to be directed against minor histocompatibility differences, it appears from our experiments with congenic mice that the activity is to some extent recognized in the context of the H-2 haplotype, since it was optimum when the NZB cells matched the target cells at the K or D end of H-2. NZB cells sensitized in vitro by H-2 identical cells were only minimally stimulated to proliferate; however, such cells were able to induce in vivo GVH reactions in NZB mice. Similar in vitro anti-H-2d reactivity was observed with NZB × W spleen cells. In contrast, spleen cells from BXSB, MRL/1, and MRL/n mice were not sensitized in vitro with H-2 identical cells. Spleen cells from all autoimmune murine strains incubated with irradiated syngeneic cells were devoid of any cytolytic activity against syngeneic target cells. Cells from all autoimmune strains sampled during youth exhibited a normal effector function against H-2 incompatible spleen cells, and this function declined moderately with age and appearance of disease. In contrast to all other autoimmune strains, cells from MRL/1 mice were inadequate stimulators with H-2 incompatible cells, possibly due to massive T cell lymphoproliferation seen in these mice. Although the observed anti-H-2d activity of cells from New Zealand mice (NZB, NZB × W) may play a role in the development of their disease, the possibility that such a mechanism serves as a common etiologic pathway in the development of the murine SLE-like syndromes seems unlikely since the other autoimmune strains studied were devoid of such activity.