Does T-cell tolerance require a dedicated antigen-presenting cell?
Almost 30 years ago Burnet proposed that the immune system maintained self-tolerance by deleting autoreactive lymphocytes. Recently it has become clear that for T cells this step occurs in the thymus, where developing T cells first express their antigen-specific receptors. Here a T-cell which encounters its antigen disappears--if it is not dead, it at least stops expressing its receptors. In the periphery by contrast, encounter with antigen leads to activation and proliferation of the responding T-cell. There are two possible explanations for this difference. Either the antigen-presenting cells in the thymus are different from those in the periphery and instead of producing positive signals they directly or indirectly kill the thymocytes; or the T cells themselves are different, and like immature B cells, may die after encounter with antigen. We tested the first possibility and found that dendritic cells from spleen, which are the most potent activators of mature T cells, are also the most potent inactivators of young developing T cells. Thus it is not the antigen-presenting cell which determines whether a T-cell responds or dies, but the T-cell itself or its thymic environment.
Matzinger
P
P
Basel Institute for Immunology, Switzerland.
Guerder
S
S
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D005333:Fetus; D007108:Immune Tolerance; D051379:Mice; D008815:Mice, Inbred Strains; D009924:Organ Culture Techniques; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000528:radiation effects; D013950:Thymus Gland / Q000276:immunology