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.