The IL-6-deficient mouse exhibits impaired lymphocytic responses to a vaccine combining live Leishmania major and CpG oligodeoxynucleotides.

We have previously reported that vaccination with CpG oligodeoxynucleotides delivered concomitantly with live Leishmania major (Lm/CpG) eliminates lesions associated with live vaccination in C57BL/6 mice. The absence of lesions is at least in part a result of the CpG DNA-mediated activation of dermal dendritic cells to produce cytokines such as interleukin (IL)-6. Wild-type C57BL/6 mice and IL-6-/- mice were immunized with the Lm/CpG vaccine and monitored for the development of lesions. IL-6-/- mice developed extensive, nonhealing lesions following live vaccination. The analysis of the inoculation site and draining lymph nodes of the IL-6-/- mice revealed a constitutive reduction in lymphocyte numbers, particularly CD4+ T cells. Live vaccination resulted in the specific expansion of CD4+Foxp3+ regulatory T cells in the knockout mice, and in a decrease of CD4+ IFN-gamma -producing cells. These results indicate that IL-6-/- mice may have collateral immune defects that could influence the development of the natural immune response to pathogens, vaccines, or other inflammatory stimuli.