CD4(-) T-CELLS ARE THE EFFECTOR-CELLS IN DISEASE PATHOGENESIS IN THE SCURFY (SF) MOUSE()CD8()

hemizygous for the X-linked mutation, scurfy (sf), exhibit a fatal lym phoreticular disease that is mediated by T lymphocytes. To evaluate th e respective roles of CD4 or CD8 single positive T cells in scurfy dis ease, neonates were treated with mAbs directed against the CD4 or CD8 molecules. Whereas mice treated with an anti-CD8 Ab developed lesions and succumbed to disease at the same time (17 days) as their untreated scurfy littermates, mice treated with an anti-CD4 Ab lived up to 11 w k before developing scurfy disease. To insure a more complete eliminat ion of the T cell subsets, the scurfy mutation was bred onto beta(2)-m icroglobulin (beta(2)m)-deficient (CD8-less) and CD4-deficient transge nic mouse lines. Whereas there was little moderation of disease in bet a(2)m-deficient scurfy mice, CD4-deficient scurfy mice had markedly de creased scurfy lesions and a prolonged life span, similar to that of a nti-CD4-treated sf/Y mice. Additionally, scurfy disease was transplant ed into H-2-compatible nude mice through the adoptive transfer of CD4( +)CD8(-) T cells, but not CD4(-)CD8(+) T cells. Flow-cytometric analys is revealed that sf/Y mice have an increased percentage of activated C D4(+) T cells in their lymph nodes. In addition, there is an increase in the in vitro production of cytokines in the cultured splenocytes of CD8-less, but not CD4-less, scurfy mice. These data suggest that CD4( +) T cells are critical mediators of disease in the scurfy mouse.