CD4(+) BUT NOT CD8(+) CELLS ARE ESSENTIAL FOR ALLOREJECTION

The generation of knockout mice with targeted gene disruption has prov ided a valuable tool for studying the immune response. Here we describ e the use of CD4 and CD8 knockout mice to examine the role of CD4(+) a nd CD8(+) cells in initiating allotransplantation rejection. Pretreatm ent with a brief course of depletive anti-CD4 monoclonal antibody ther apy allowed permanent survival of heart, but not skin, allografts tran splanted across a major histocompatibility barrier. However, skin as w ell as heart grafts were permanently accepted in the CD4 knockout mice . Transfer of CD4(+) cells into CD4 knockout recipient mice 1 d before skin engraftment reconstituted rejection, demonstrating that CD4(+) c ells are necessary for initiating rejection of allogeneic transplants. Major histocompatibility complex disparate heart and skin allografts transplanted into CD8 knockout recipients were rejected within 10 d. T his study demonstrates that CD4(+) but not CD8(+) T cells are absolute ly required to initiate allograft rejection.