Dominant transplantation tolerance impairs CD8+ T cell function but not expansion.
Alloreactive CD8+ T cells may persist in animals made tolerant of transplanted tissues; their function is controlled through continuous censorship by regulatory CD4+ T cells. We sought to establish the stage at which such censorship operates. We found that monospecific CD8+ T cells introduced into tolerant animals responded to the tolerated tissue antigen as if they had received CD4+ T cell "help": they proliferated and accumulated normally. However, they did show compromised graft rejection, interferon-gamma production and cell-mediated cytotoxicity. These findings suggest that tolerance mediated by regulatory T cells acts by censoring immune effector functions rather than by limiting the induction of T cell responses.
Lin
Chun-Yen
CY
Sir William Dunn School of Pathology, University of Oxford, UK.
Graca
Luis
L
Cobbold
Stephen P
SP
Waldmann
Herman
H
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D006084:Graft Rejection / Q000276:immunology; D006085:Graft Survival / Q000276:immunology; D007108:Immune Tolerance; D007371:Interferon-gamma / Q000276:immunology; D007519:Isoantigens / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D016377:Organ Transplantation; D014181:Transplantation Immunology
D007519:Isoantigens; D007371:Interferon-gamma