This is suggestive of two possible mechanisms of signalling (i) IL-4 signalling via IL-4Rα is antagonistic to IFN-γ dependent [63] or independent [64] B cell IgG2a isotype class switching retarding both control vaccine and IL-13R adjuvant vaccine IgG2a responses. Whereas, with the IL-4C118 adjuvant vaccine IL-4 is unable to stimulate cell signalling resulting in enhanced and early HIV gag/pol specific IgG2a isotype switching following prime-boost vaccination. (ii) Alternatively, signalling Trichostatin A clinical trial via the IL-13Rα2 receptor in the absence of IL-4Rα signalling can influence B cell maturation and IgG2a class switching during

the Th1 influenced humoral response. Collectively, the data indicate that these IL-4/IL-13 receptors are important players in modulating protective immunity. Our previous studies have shown that rFPV is an excellent mucosal delivery vector compared to rVV [19], [20] and [40] and the priming

immunisation determines the avidity of the CD8+ T cell repertoire induced [23]. We have recently completed an analysis of lung-derived DC (LDC) subsets induced 24 h following intranasal immunisation of mice BMS-354825 manufacturer [80]. Interestingly, unlike other pox viral vectors tested rFPV priming was shown to induce a unique CD11b+ CD103− LDC population and

adoptive transfer studies demonstrated that the unlike CD103+ LDC the CD103− LDC population favoured the induction of high avidity CD8 T cells following immunisation. Interestingly, both the IL-13Rα2 and IL-4C118 adjuvant vaccines induced higher numbers of the CD11b+ CD103− LDC population relative to the control which correlated with proliferation of high magnitude, strong avidity HIV specific CD8+ T cell responses and protective immunity. Differences in CD11b− B200+ and CD11b− CD8+ LDC subsets were also detected between the IL-13Rα2 and IL-4C118 adjuvant vaccines. These changes in the LDC populations are indicative of the effects of endogenous IL-4/IL-13 are of influencing the innate immune response, imprinting the quality of the downstream adaptive cell mediated and humoral immune outcomes [80]. These observations and the current results raise the question; what is the source of IL-13 during the innate response? While IL-13 and IL-4 are traditionally thought to be expressed by Th2 CD4+ cells, recent studies have identified an additional important cellular source of IL-13 early in the immune response. Innate lymphoid cells (ILC) are emerging as central effectors of innate and adaptive immunity and tissue remodelling [65] and [66].