Induction of T cell anergy in the absence of CTLA-4/B7 interaction.
Immunologic tolerance in T lymphocytes is maintained through both thymic and peripheral contributions. One peripheral tolerance mechanism is the induction of T cell anergy, a form of nonresponsiveness resulting from incomplete T cell activation, such as stimulation through the TCR in the absence of costimulation. Recent reports have suggested that engagement of the inhibitory receptor CTLA-4 by its B7 ligand is critical for the initiation of anergy. We tested the importance of CTLA-4 in anergy induction in primary T cells with an in vitro anergy system. Using both CTLA-4/B7-blocking agents and CTLA-4-deficient T cells, we found that T cell anergy can be established in the absence of CTLA-4 expression and/or function. Even in the absence of CTLA-4 signal transduction, T cells activated solely through TCR ligation lose the ability to proliferate as a result of autocrine IL-2 production upon subsequent receptor engagement. Thus, CTLA-4 signaling is not required for the development of T cell anergy.
Frauwirth
K A
KA
Abramson Family Cancer Research Institute and Department of Cancer Biology, University of Pennsylvania, Philadelphia, PA 19104, USA.
Alegre
M L
ML
Thompson
C B
CB
D000069594:Abatacept; D000595:Amino Acid Sequence; D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D000943:Antigens, Differentiation / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D018122:B7-1 Antigen / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051940:B7-2 Antigen; D060908:CTLA-4 Antigen; D002460:Cell Line; D017635:Clonal Anergy / Q000235:genetics; D002999:Clone Cells; D005260:Female; D018796:Immunoconjugates; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*
D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D060908:CTLA-4 Antigen; C497965:Cd86 protein, mouse; C556707:Ctla4 protein, mouse; D018796:Immunoconjugates; D008562:Membrane Glycoproteins; D000069594:Abatacept