REDUCED DEVELOPMENT OF CD4(-)8(-)B220(-CELLS BUT NORMAL AUTOANTIBODY PRODUCTION IN LPR() T)LPR MICE LACKING MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I MOLECULES/

The lpr gene has recently been shown to encode a functional mutation i n the Fas receptor, a molecule involved in transducing apoptotic signa ls. Mice homozygous for the lpr gene develop an autoimmune syndrome ac companied by massive accumulation of double-negative (DN) CD4(-)8-B220 (+) T cell receptor-alpha/beta(+) cells. In order to investigate the o rigin of these DN T cells, we derived lpr/lpr mice lacking major histo compatibility complex (MHC) class I molecules by intercrossing them wi th (beta 2-microglobulin (beta 2m)-deficient mice. Interestingly, thes e lpr beta 2m-/- mice develop 13-fold fewer DN T cells in lymph nodes as compared to lpr/lpr wild-type (lprWT) mice. Analysis of anti-DNA an tibodies and rheumatoid factor in serum demonstrates that lpr beta 2m- /- mice produce comparable levels of autoantibodies to lprWT mice. Col lectively our data indicate that MHC class I molecules control the dev elopment of DN T cells but not autoantibody production in lpr/lpr mice and support the hypothesis that the majority of DN T cells may be der ived from cells of the CD8 lineage.