ROLE OF INFUSED CD8(+) CELLS IN THE INDUCTION OF PERIPHERAL TOLERANCE

The CD8 molecule when present on a cell recognized by a mature T cell has been shown to have an inhibitory effect on the development of an i n vitro immune response by that T cell. To test whether CD8 has a role in the induction of peripheral tolerance in vivo, we have studied tol erance induction in B6 female mice carrying a transgenic TCR specific to male H-Y Ag. Previous studies have shown that male Ag reactive cell s are inactivated in these mice after the i.v. injection of viable mal e lymphoid cells. Here, B6 female transgenic mice were injected with B 6 male lymph node cells from CD4 or CD8 gene knockout mice, and the fa te of male Ag-specific T cells was followed in vivo. Our results indic ate that injection of male CD4 knockout (express CD8) lymphoid cells b ut not CD8 knockout (do not express CD8) lymphoid cells induced a sign ificant reduction of male H-Y Ag reactive cells in the periphery, sugg esting that CD8 plays an important role in the induction of peripheral tolerance of class I-restricted T cells. These results imply that per ipheral tolerance can be induced not just by absence of signals requir ed for activation but by the presence of additional signals.