THE MAJORITY OF POSTSELECTION CD4(-POSITIVE THYMOCYTES REQUIRES THE THYMUS TO PRODUCE LONG-LIVED, FUNCTIONAL T-CELLS() SINGLE)

We have previously isolated, and characterized in vitro, two subsets o f CD4(hi) T cell receptor (TCR)(hi) single positive (SP) thymocytes: C D8(-) and CD8(lo). In this report, we have analyzed phenotypic, functi onal, and developmental characteristics of these ''late'' CD4(hi) SP t hymocyte subsets. The TCR(hi) phenotype and the elimination of T cells expressing TCR V-beta segments reactive with endogenous mouse mammary tumor virus (MMTV) products suggested that both subsets had undergone positive and negative selection. CD8-4(hi)-thymocytes were functional , as judged by their ability to: (a) induce lethal graft versus host d isease (GVHD); (b) survive and expand in peripheral lymphoid organs; a nd (c) proliferate, rather than undergo apoptosis, in response to in v itro TCR cross-linking. By contrast, CD8(lo)4(hi) cells could not indu ce GVHD, were unable to expand (and perhaps even survive) in periphera l organs and underwent apoptosis upon TCR cross-linking. However, when reintroduced into the thymus, these cells matured into functional, lo ng-lived CD8-4(hi) lymphocytes. These results document an obligatory r equirement for the thymic microenvironment in the final maturation of the majority of CD4(hi) SP postselection thymocytes, and demonstrate t he existence of a previously unrecognized control point in T cell deve lopment.