A T-CELL ACTIVATION ANTIGEN, LY6C, INDUCED ON CD4(-2 AND PROLIFERATION IN PERIPHERAL IMMUNE-RESPONSES() TH1 CELLS MEDIATES AN INHIBITORY SIGNAL FOR SECRETION OF IL)

A T cell activation antigen, Ly6C, is considered to be involved in the autoimmunity of some autoimmune-prone mice; however, the function of Ly6C remains largely unknown. We prepared a rat anti-mouse Ly6C monocl onal antibody (mAb) (S14) that inhibits the proliferation of periphera l T cells stimulated with anti-CD3 mAb in vitro. S14 mAb, the specific ity of which is confirmed by a cDNA transfectant, recognizes Ly6C anti gen preferentially expressed on a part of CD8(+) T cells in peripheral lymphoid organs. The immunohistochemical analysis demonstrates that L y6C appears on CD8(+) T cells in the conventional T cell-associated ar ea of BALB/c but not of nonobese diabetic (NOD) mice, confirming the a bsence of Ly6C(+) T cells in NOD mice. Addition of soluble S14 mAb to the culture does not influence the proliferation of T cells in vitro; however, the S14 mAb coated on the plate clearly inhibits the prolifer ation and IL-2 production of anti-CD3-stimulated peripheral T cells. T he T cells are arrested at the transitional stage from G(0)/G(1) to SG(2)/M phases, but they are not induced to undergo apoptotic changes i n vitro. This inhibitory signal provided through the Ly6C molecule inh ibited IL-2 secretion in a subpopulation of the activated CD4(+) T cel ls. Ly6C is expressed on T cell clones of both Th1 and Th2 cells, but the cytokine secretion from Th1 clones is preferentially inhibited. Th ese results suggest that Ly6C mediates an inhibitory signal for secret ion of cytokines from Th1 CD4(+) T cells, potentially causing the inhi bition of immune response in peripheral lymphoid tissues.