Constitutive expression of Bcl-xL or Bcl-2 prevents peptide antigen-induced T cell deletion but does not influence T cell homeostasis after a viral infection.
We examined the CD8+ T cell response to lymphocytic choriomeningitis virus (LCMV) in mice doubly transgenic for an LCMV-specific TCR and for either bcl-xL or bcl-2. Clonal down-sizing of the anti-viral CD8+ T cell response and the generation of T cell memory was not influenced by constitutive expression of these anti-apoptotic proteins in T cells. Expression of Bcl-xL or Bcl-2 did, however, prevent LCMV peptide-induced peripheral deletion of mature CD8+ T cells in vivo and apoptosis of activated LCMV-specific effector T cells in vitro. The CD8+ T cells "rescued" by Bcl-xL or Bcl-2 from peptide antigen-induced cell death were anergic and this could not be reversed by addition of IL-2 in vitro or by adoptive transfer into antigen-free recipient mice followed by LCMV infection in vivo. Taken together, we show here that 1) Bcl-xL or Bcl-2 are functionally equivalent in their ability to modulate CD8+ T cell survival in vivo, 2) distinct apoptosis signaling pathways exist in CD8+ T cells, one that can be inhibited by Bcl-2 or Bcl-xL and one that cannot be blocked, and 3) apoptosis of CD8+ effector T cells during the declining phase of an immune response is not prevented by constitutive expression of the anti-apoptotic proteins Bcl-xL and Bcl-2.
Petschner
F
F
Institute for Medical Microbiology and Hygiene, Department of Immunology, University of Freiburg, Germany.
Zimmerman
C
C
Strasser
A
A
Grillot
D
D
Nunez
G
G
Pircher
H
H
D000818:Animals; D000956:Antigens, Viral; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002470:Cell Survival / Q000235:genetics / Q000276:immunology; D017635:Clonal Anergy / Q000235:genetics; D017637:Clonal Deletion / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D005786:Gene Expression Regulation / Q000276:immunology; D006023:Glycoproteins / Q000008:administration & dosage / Q000276:immunology*; D006706:Homeostasis / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D007274:Injections, Intraperitoneal; D008216:Lymphocytic Choriomeningitis / Q000235:genetics / Q000276:immunology*; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000008:administration & dosage / Q000096:biosynthesis* / Q000235:genetics; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism*; D019076:Transgenes / Q000276:immunology; D014764:Viral Proteins; D051020:bcl-X Protein
D000956:Antigens, Viral; C494812:Bcl2l1 protein, mouse; D006023:Glycoproteins; D010446:Peptide Fragments; D019253:Proto-Oncogene Proteins c-bcl-2; D014764:Viral Proteins; D051020:bcl-X Protein; C094244:glycoprotein peptide 33-41, Lymphocytic choriomeningitis virus