Immunisation route-dependent expression of IL-4/IL-13 can modulate HIV-specific CD8(+) CTL avidity
Date
2009
Authors
Ramshaw, Ian
Ranasinghe, Charani
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Publisher
Wiley-VCH Verlag GMBH
Abstract
All HIV-1 'systemic vaccine trials'-in humans have yielded poor outcomes. Thus, it is important to understand whether the route of delivery influences the quality of protective CTL immunity. Using heterologous poxvirus immunisation we have shown that systemically (i.m./ i.m.) immunised CD8+ T cells generated higher levels of IL-4/ IL-13 compared to mucosal delivery and expression also correlated with i.m./i.m. immunised mice eliciting CTL of lower avidity. Studies using IL-4-/- and IL-13-/- KO mice have shown that the capacity to express IFN-γ, IL-4 and/or IL-13 by KdGag197-205-specific CTL differed between these groups and was inversely correlated with CTL avidity (IL-13-/-> IL-4-/->BALB/c), although no significant differences in the magnitude of CTL responses were observed between IL-13-/- and wild type mice. When IL-13 was reconstituted in IL-13-/- splenocytes in vitro, their ability to bind tetramers also decreased significantly. Our data reveal that total absence of IL-13 can greatly enhance CTL avidity. In contrast, extracellular IL-4 appears to be important in maintaining long-term Th1/Th2 balance in CTL, even though expression of IL-4 by CTL markedly reduced avidity. STAT6-/- mice also showed memory CTL of higher avidity. Furthermore, CCL5 expression in KdGag197-205-specific CTL was also regulated by IL-4/IL-13.
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Keywords
Keywords: gamma interferon; interleukin 13; interleukin 4; interleukin 4 receptor alpha; RANTES; recombinant vaccine; STAT6 protein; tetramer; virus vaccine; animal cell; animal experiment; article; Bagg albino mouse; binding affinity; CD8+ T lymphocyte; controlled Avidity; CCL5; HIV-1; IL-4/IL-13; Mucosal vaccines
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Source
European Journal of Immunology
Type
Journal article
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2037-12-31