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.
Wu
Wenhui
W
James A. Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
Weigand
Luise
L
Mendez
Susana
S
D000818:Animals; D015850:Interleukin-6 / Q000172:deficiency* / Q000235:genetics; D018320:Leishmania major / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000276:immunology* / Q000469:parasitology; D018655:Lymphocyte Count; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage / Q000276:immunology*; D016052:Protozoan Vaccines / Q000008:administration & dosage / Q000276:immunology*; D014611:Vaccination; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000276:immunology
C408982:CPG-oligonucleotide; D015850:Interleukin-6; D009838:Oligodeoxyribonucleotides; D016052:Protozoan Vaccines; D014613:Vaccines, Attenuated