Aberrant induction of T cell tolerance in B cell suppressed mice.
Self-tolerance is the process by which the T cell repertoire develops without expressing self-reactive specificities. The mechanisms which functionally eliminate self-reactive T cells are clonal deletion and clonal inactivation, and both of these phenomena have been studied in T cell populations reactive to endogenous superantigens that are encoded by endogenous mouse mammary tumor proviruses (Mtv). The studies described here demonstrate that the kinetics of Etc-1 (encoded by the Mtv-9 open reading frame gene)-mediated deletion are much slower than that seen for Mls 1a (encoded by the Mtv-7 open reading frame), and that Etc-1-reactive T cells are present in the periphery up to 2 wk after birth. The deletion of peripheral Etc-1-reactive T cells late in ontogeny indicates an efficient mechanism of peripheral clonal deletion in these animals. The clonal deletion of Etc-1-reactive cells is abrogated in B cell-suppressed animals; however, clonal elimination of peripheral V beta 5+ or V beta 11+ (Etc-1 reactive) T cells can be induced when these mice are allowed to recover their B cell population after cessation of anti-mu treatment. Finally, we establish that peripheral Etc-1-reactive V beta 11+/CD4+ T cells remaining in B cell-suppressed and recovering animals are markedly less responsive to stimulation through the TCR than are control T cells. These data support the idea that peripheral self-reactive T cells can be rendered tolerant by two mechanisms which may be temporally related. This model suggests that clonal hyporesponsiveness may be followed by clonal deletion.
Gollob
K J
KJ
Department of Pediatrics, National Jewish Center for Immunology and Respiratory Medicine, Denver, CO 80206.
Palmer
E
E
D000818:Animals; D000831:Animals, Newborn; D000956:Antigens, Viral / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D015704:CD4 Antigens / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D007108:Immune Tolerance; D051379:Mice; D008810:Mice, Inbred C57BL; D016747:Minor Lymphocyte Stimulatory Antigens / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis; D013601:T-Lymphocytes / Q000276:immunology*
D000956:Antigens, Viral; D015704:CD4 Antigens; D016827:CD8 Antigens; D016747:Minor Lymphocyte Stimulatory Antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta