Stronger correlation of bcl-3 than bcl-2, bcl-xL, costimulation, or antioxidants with adjuvant-induced T cell survival.
A set of signals separate from those needed for T cell activation and clonal expansion acts to sustain a T cell response once it has begun. Immunologic adjuvants can initiate these signals in a process we designate adjuvant-induced survival (AIS). Here, the natural adjuvant LPS was used in a super-antigen model of AIS to understand which factors are needed to sustain T cell survival after activation. Flow cytometric stains for antiapoptotic Bcl-2 and Bcl-xL showed that neither factor was well correlated with AIS, although both were increased transiently upon T cell activation. T cells protected via AIS showed no increased ability to resist death caused by reactive oxygen species, and cellular division was not accelerated as might be expected if AIS were to operate through co-stimulatory pathways. Finally, microarray analyses were performed that showed increased expression of Bcl-3, an NFkappaB/IkappaB factor, was correlated with AIS. It is proposed that T cell survival during productive immune responses occurs by successive activities of Bcl-2, Bcl-xL and Bcl-3, with Bcl-3 requiring innate immune responses to adjuvants for its expression.
Mitchell
Thomas C
TC
Institute for Cellular Therapeutics, University of Louisville School of Medicine, Louisville, Kentucky 40202, USA. tom.mitchell@louisville.edu
Teague
T Kent
TK
Hildeman
David A
DA
Bender
Jeremy
J
Rees
William A
WA
Kedl
Ross M
RM
Swanson
Brad
B
Kappler
John W
JW
Marrack
Philippa
P
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D000081242:B-Cell Lymphoma 3 Protein; D002455:Cell Division; D002470:Cell Survival / Q000187:drug effects; D020869:Gene Expression Profiling; D019254:Genes, bcl-2; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation; D051379:Mice; D018448:Models, Immunological; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D018089:Superantigens / Q000494:pharmacology; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D014157:Transcription Factors; D051020:bcl-X Protein
D000276:Adjuvants, Immunologic; D000975:Antioxidants; D000081242:B-Cell Lymphoma 3 Protein; C494812:Bcl2l1 protein, mouse; C000631345:Bcl3 protein, mouse; D008070:Lipopolysaccharides; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D018089:Superantigens; D014157:Transcription Factors; D051020:bcl-X Protein