The role of alpha beta(+) T cells and homeostatic T cell proliferation in Y-chromosome-associated murine lupus

Male BXSB mice develop an early life, severe lupus-like disease largely att ributed to an undefined Y-chromosome-associated autoimmunity accelerator, t ermed Yaa. Although the exact disease pathogenesis is uncertain, indirect e vidence suggests that T cells play an important role in the male BXSB disea se. We have developed TCR alpha -chain gene-deleted BXSB mice to directly e xamine the role of alpha beta (+) T cells and the mode by which Yaa promote s disease in this strain. All disease parameters, including hypergammaglobu linemia, autoantibody production, glomerulonephritis, and the unique monocy tosis of BXSB males, were severely reduced or absent in the alpha beta (+) T cell-deficient mice. Adoptively transferred CD4(+) T cells of either male or female BXSB origin showed equal homeostatic proliferation in alpha beta (+) T cell-deficient male recipients. Moreover, deficient male mice eventu ally developed equally severe lupus-like disease after adoptive transfer an d homeostatic expansion of T cells from wild-type BXSB males or females. Th e results directly demonstrate that the Yaa-mediated disease requires alpha beta (+) T cells that are not, in themselves, abnormal in either compositi on or properties, but are engaged by a Yaa-encoded abnormality in a non-T c ell component. In addition, homeostatic anti-self proliferation of mature T cells derived from a small number of precursors can induce systemic autoim munity in an appropriate background.