Differential control of autoantibodies and lymphoproliferation by Fas ligand expression on CD4(+) and CD8(+) T cells in vivo

We have previously shown that the gld autoimmune syndrome is suppressed in lethally irradiated gld mice reconstituted with a mixture of normal and gld bone marrow (BM), Furthermore, in vivo depletion of normal Thy-1(+) cells restores lymphoproliferation and autoantibody production in such chimeras, suggesting that T cells bearing Fas ligand are responsible for correcting t he gld defect. In this study, mixed-BM chimeras lacking either normal CD4() (B6CD4KO-B6gld) or normal CD8(+) T cells (B6CD8KO-B6gld) were generated t o determine the contribution of the normal T cell subsets to disease suppre ssion. Lymphoproliferation was completely suppressed in BGCD4KO-B6gld chime ras but only modestly in B6CD8KO-B6gld chimeras. On the other hand, both ty pes of mixed-BM chimeras had incomplete effects on the suppression of serum autoantibodies when compared with B6gld reconstituted with isologous BM, T hese results suggest that both T cell subsets provide Fas ligand to suppres s immune cells responsible for autoantibody production; however, CD8(+) T c ells are mainly responsible for preventing lymphoproliferation.