Antigen activation rescues recent thymic emigrants from programmed cell death in the BB rat.
One of the diabetes susceptibility genes of the BB rat is a mutation at the lyp locus that decreases the thymic output of T cells and the life span of most recent thymic emigrants (RTE). Consequently, there is a 10-fold reduction in the number of CD4+ and CD8+ T cells in secondary lymphoid organs. Results presented in this work demonstrate that the BB rat lyp mutation is associated with an accelerated apoptotic death in vitro of mature CD4+ 8- and CD4- 8+ thymocytes and peripheral T cells. The stability of the pool of recirculating T cells (PRL) of BB rats over time results from a > 10-fold increase in the mitotic activity of T cells as assessed in vivo by bromodeoxyuridine incorporation. This increased mitotic activity is not observed when BB T cells develop in the context of a normal sized PRL. MHC haploidentical WF and BB rats differ at minor histocompatibility loci. Intravenous injection of (WF x BB)F1 T cells into euthymic BB rats led to the rejection of donor T cells within 3 wk by unprimed recipients and within 1 wk by primed recipients. This secondary immune response was unaffected by postpriming thymectomy. F1 T cells were not rejected, but rather expanded after their injection into thymectomized BB rats that had been primed as early as 48 h after thymectomy. These results strongly suggest that the BB rat PRL is devoid of long-lived naive T cells and that rescue of recent thymic emigrants from programmed cell death is initiated by Ags, exclusively.
Ramanathan
S
S
Department of Medicine, University of Toronto, Ontario, Canada.
Norwich
K
K
Poussier
P
P
D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D016922:Cellular Senescence / Q000276:immunology; D008231:Lymphopenia / Q000276:immunology; D008938:Mitosis; D051381:Rats; D011913:Rats, Inbred BB / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology* / Q000502:physiology; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology*