title: Cleavage of anti-apoptotic Bcl-2 family members after TCR stimulation contributes to the decision between T cell activation and apoptosis.
abstract: Engagement of the TCR induces activation-induced cell death (AICD) of T cells that have been previously stimulated. However, a portion of these T cells can survive and undergo further activation. The molecular mechanism that decides whether a T cell will live or die after TCR re-engagement is unclear. We found that cross-linking of TCR in preactivated primary mouse T cells led to the cleavage of anti-apoptotic Bcl-2 and Bcl-xL in dying cells. Cleavage-resistant Bcl-2 and Bcl-xL were more efficient than their wild-type counterparts in the inhibition of apoptosis in primary mouse T cells and in the H9 T cell line after TCR cross-linking. In contrast, the surviving T cells after TCR re-engagement displayed upregulation of Bcl-xL, and knockdown of Bcl-xL promoted AICD. This indicates that caspase-mediated cleavage of anti-apoptotic Bcl-2 or Bcl-xL facilitates AICD in T cells, whereas upregulation of Bcl-xL promotes T cell survival and allows further T cell activation. Our data suggest that cleavage of anti-apoptotic Bcl-2 and Bcl-xL contributes to the decision between T cell activation and apoptosis after TCR re-engagement.
authors.affiliation: Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Alan D
authors.initials: AD
authors.lastname: Guerrero
authors.forename: Robert L
authors.initials: RL
authors.lastname: Welschhans
authors.forename: Min
authors.initials: M
authors.lastname: Chen
authors.forename: Jin
authors.initials: J
authors.lastname: Wang
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism* / Q000502:physiology; D016923:Cell Death / Q000276:immunology; D002460:Cell Line; D002470:Cell Survival / Q000276:immunology; D006801:Humans; D006868:Hydrolysis; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D019463:Mice, Inbred MRL lpr; D005810:Multigene Family / Q000276:immunology*; D061251:Primary Cell Culture; D011518:Proto-Oncogene Proteins / Q000378:metabolism* / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism* / Q000502:physiology; D020239:Receptor Cross-Talk / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism / Q000502:physiology*; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D051020:bcl-X Protein / Q000378:metabolism* / Q000502:physiology
chemical_list: D051017:Apoptosis Regulatory Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011948:Receptors, Antigen, T-Cell; D051020:bcl-X Protein; C052617:Bcl2 protein, mouse