CD8 T cells require Bcl-3 for maximal gamma interferon production upon secondary exposure to antigen.
Adjuvant-induced survival of T cells after antigen activation correlates with increased expression of Bcl-3. Bcl-3 is an NF-kappaB/IkappaB family member and has been implicated in transcriptional regulation in several cell types. We tested the ability of mice deficient in Bcl-3 (Bcl-3 KO) to exhibit T-cell adjuvant-induced survival after challenge with the superantigen staphylococcal enterotoxin B (SEB), using lipopolysaccharide (LPS) as a natural adjuvant. These studies showed that Bcl-3 is required for secondary gamma interferon (IFN-gamma) production by CD8 T cells but not for adjuvant-induced survival effects. Specifically, wild-type and Bcl-3 KO mice exhibited comparable long-term increases in the Vbeta8(+) T-cell populations, indicating no lack of survival in response to adjuvant stimulation in the Bcl-3 KO activated T cells. Ectopic expression of the Bcl-3-related molecules IkappaBalpha, IkappaBbeta, and IkappaBepsilon in SEB-activated T cells increased survival during in vitro culture in the absence of adjuvant, suggesting that these IkappaB molecules could exert a survival function in antigen-activated T cells in place of Bcl-3. However, Vbeta8(+) CD8 T cells from SEB- plus LPS-treated Bcl-3 KO mice produced less IFN-gamma upon in vitro restimulation than Vbeta8(+) CD8 T cells from wild-type mice. Therefore, Bcl-3 plays a unique role in the regulation of IFN-gamma production in this model system.
Chilton
Paula M
PM
Institute for Cellular Therapeutics, University of Louisville, 570 South Preston Street, Suite 404, Louisville, KY 40202-1760, USA.
Mitchell
Thomas C
TC
D000818:Animals; D000941:Antigens / Q000276:immunology*; D000081242:B-Cell Lymphoma 3 Protein; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D002470:Cell Survival / Q000276:immunology; D004768:Enterotoxins / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011518:Proto-Oncogene Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000276:immunology; D014157:Transcription Factors
D000941:Antigens; D000081242:B-Cell Lymphoma 3 Protein; C000631345:Bcl3 protein, mouse; D004768:Enterotoxins; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors; C031818:enterotoxin B, staphylococcal; D007371:Interferon-gamma