Inflammatory cytokines overcome age-related defects in CD4 T cell responses in vivo.
Age-related decreases in immune function are thought to contribute to the reduced efficacy of vaccinations seen in elderly populations. Our previous in vitro studies demonstrated that naive CD4 T cells from aged TCR-transgenic mice proliferate less than young cells and generate poorly functioning effectors due to decreased IL-2 production. In this current study, we show that this age-related defect in CD4 T cell response also occurs in vivo and that it is correlated with reduced NF-kappa B activation. After transfer to young hosts, CD4 T cells from aged transgenic mice proliferate less and produce reduced levels of IL-2 upon immunization with Ag and alum. Introducing a combination of the inflammatory cytokines TNF-alpha, IL-1, and IL-6, or the use of an adjuvant such as CFA that induces these cytokines, markedly enhanced responses of these aged CD4 T cells, so that they proliferated and produced IL-2 similar to young cells. This enhancement is correlated with the enhanced activation of the transcription factor NF-kappa B in aged cells. We suggest that induction of inflammatory cytokines via adjuvants may enhance the efficacy of vaccinations in elderly populations.
Haynes
Laura
L
Trudeau Institute, Saranac Lake, NY 12983, USA. lhaynes@trudeauinstitute.org
Eaton
Sheri M
SM
Burns
Eve M
EM
Rincon
Mercedes
M
Swain
Susan L
SL
D019264:Adoptive Transfer; D000375:Aging / Q000235:genetics / Q000276:immunology; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D002455:Cell Division / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000235:genetics / Q000276:immunology*; D016207:Cytokines / Q000008:administration & dosage / Q000096:biosynthesis / Q000502:physiology*; D015536:Down-Regulation / Q000276:immunology; D016130:Immunophenotyping; D018836:Inflammation Mediators / Q000008:administration & dosage / Q000494:pharmacology*; D007376:Interleukin-2 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010455:Peptides / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology
D016207:Cytokines; D018836:Inflammation Mediators; D007376:Interleukin-2; D010455:Peptides; D014157:Transcription Factors