PERIPHERAL T-CELL SURVIVAL REQUIRES CONTINUAL LIGATION OF THE T-CELL RECEPTOR TO MAJOR HISTOCOMPATIBILITY COMPLEX-ENCODED MOLECULES

In the thymus, T cells are selected according to their T cell receptor (TCR) specificity. After positive selection, mature cells are exporte d from primary lymphoid organs to seed the secondary lymphoid tissue. An important question is whether survival of mature T cells is an intr insic property or requires continuous survival signals, i.e., engageme nt of the TCP by major histocompatibility complex (MHC) molecules in t he periphery, perhaps in a similar way as occurring during thymic posi tive selection. To address this issue we used recombination-activating gene (Rag)-deficient H-2(b) mice expressing a transgenic TCR restrict ed by I-Ed class II MHC molecules. After engraftment with Rag(-/-) H-2 (d) fetal thymi, CD4(+)8(-) peripheral T cells emerged. These cells we re isolated and transferred into immunodeficient hosts of H-2(b) or H- 2(d) haplotype, some of the latter being common cytokine receptor gamm a chain deficient to exclude rejection of H-2(b) donor cells by host n atural killer cells. Our results show that in the absence, but not in the presence, of selecting MHC molecules, peripheral mature T cells ar e short lived and disappear within 7 wk, indicating that continuous co ntact of the TCR with selecting MHC molecules is required for survival of T cells.