Cutting edge: contributions of apoptosis and anergy to systemic T cell tolerance.
Multiple pathways can induce and maintain peripheral T cell tolerance. The goal of this study was to define the contributions of apoptosis and anergy to the maintenance of self-tolerance to a systemic Ag. Upon transfer into mice expressing OVA systemically, OVA-specific DO11 CD4+ T cells are activated transiently, cease responding, and die. Bim is the essential apoptosis-inducing trigger and apoptosis proceeds despite increased expression of Bcl-2 and Bcl-x. However, preventing apoptosis by eliminating Bim does not restore proliferation or cytokine production by DO11 cells. While Foxp3 is transiently induced, anergy is not associated with the stable development of regulatory T cells. Thus, apoptosis is dispensable for tolerance to a systemic self-Ag and cell-intrinsic anergy is sufficient to tolerize T cells.
Barron
Luke
L
Department of Pathology, University of California, San Francisco, CA 94143, USA.
Knoechel
Birgit
B
Lohr
Jens
J
Abbas
Abul K
AK
D019264:Adoptive Transfer; D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000276:immunology*; D051017:Apoptosis Regulatory Proteins / Q000008:administration & dosage / Q000172:deficiency / Q000235:genetics; D000072224:Bcl-2-Like Protein 11; D002470:Cell Survival / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D002645:Chickens; D017635:Clonal Anergy / Q000235:genetics / Q000276:immunology*; D017637:Clonal Deletion / Q000235:genetics / Q000276:immunology*; D008565:Membrane Proteins / Q000008:administration & dosage / Q000172:deficiency / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008928:Mitochondria / Q000276:immunology / Q000378:metabolism; D010047:Ovalbumin / Q000235:genetics / Q000276:immunology; D011518:Proto-Oncogene Proteins / Q000008:administration & dosage / Q000172:deficiency / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D012995:Solubility; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation
D051017:Apoptosis Regulatory Proteins; D000072224:Bcl-2-Like Protein 11; C000606776:Bcl2l11 protein, mouse; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D010047:Ovalbumin