Uncoupling of proliferative potential and gain of effector function by CD8(+) T cells responding to self-antigens.
Professional antigen-presenting cells (APCs) are capable of transporting self-antigens from peripheral tissues to secondary lymphoid organs where they are presented to potentially autoreactive CD8(+) T cells. In the absence of an inflammatory response, this results in immune tolerance. The presence of activated, antigen-specific CD4(+) T cells converts this tolerogenic encounter into an immunogenic one by promoting extensive proliferation of CD8(+) T cells and their development into effectors. Surprisingly, activation of APCs with an agonistic antibody specific for CD40 could not substitute for CD4(+) help in this task. Anti-CD40 induced recruitment of dendritic cells expressing high levels of B7 costimulatory molecules into the lymph nodes, which in turn, greatly enhanced activation and expansion of CD8(+) T cells. However, these activated CD8(+) cells did not demonstrate effector function. We conclude that proliferative potential and gain of effector function are separable events in the differentiation program of CD8(+) T cells.
Hernández
Javier
J
Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Aung
Sandra
S
Marquardt
Kristi
K
Sherman
Linda A
LA
D000818:Animals; D001324:Autoantigens / Q000276:immunology*; D018122:B7-1 Antigen / Q000502:physiology; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology; D019013:CD40 Antigens / Q000502:physiology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003920:Diabetes Mellitus / Q000209:etiology; D007108:Immune Tolerance; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000494:pharmacology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D011948:Receptors, Antigen, T-Cell / Q000502:physiology
D001324:Autoantigens; D018122:B7-1 Antigen; D019013:CD40 Antigens; D011948:Receptors, Antigen, T-Cell; D018664:Interleukin-12; D007371:Interferon-gamma