Clonal anergy is induced in vitro by T cell receptor occupancy in the absence of proliferation.
Murine Th1 clones that receive signals through their TCR in the absence of APC-derived co-stimulatory signals do not produce IL-2 and instead become anergic, i.e., they are subsequently unable to produce IL-2 in response to Ag and normal APC. The critical cellular event required to prevent the induction of this anergic state appears to be T cell proliferation. Anergy was induced when T cell clones were stimulated under conditions where both TCR occupancy and costimulatory signals were provided but where proliferation in response to the IL-2 produced was prevented. Once induced, anergy could be reversed if the T cells were allowed to undergo multiple rounds of cell division. These results show that anergy is induced as a consequence of TCR occupancy in the absence of cell division; this can be achieved either by limiting IL-2 production because of deficient provision of co-stimulatory signals or by preventing response to IL-2.
DeSilva
D R
DR
Department of Microbiology, University of Minnesota Medical School, Minneapolis 55455.
Urdahl
K B
KB
Jenkins
M K
MK
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D000941:Antigens / Q000276:immunology*; D003574:Cytochrome c Group / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D007108:Immune Tolerance; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000502:physiology; D007377:Interleukin-3 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D051379:Mice; D008815:Mice, Inbred Strains; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D015375:Receptors, Interleukin-2 / Q000502:physiology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D000941:Antigens; D003574:Cytochrome c Group; D007376:Interleukin-2; D007377:Interleukin-3; D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2