Interleukin-6 and interleukin-12 participate in induction of a type 1 protective T-cell response during vaccination with a tuberculosis subunit vaccine.
We examined the role of cytokines in the development of gamma interferon (IFN-gamma)-secreting protective T cells following immunization with a culture filtrate subunit vaccine against Mycobacterium tuberculosis containing the adjuvant dimethyldioctadecylammonium bromide (DDA). Depletion of either interleukin-6 (IL-6) or IL-12 with specific neutralizing antibodies during vaccination reduced the priming of T cells for antigen-specific proliferation and IFN-gamma secretion. Such reduction was also observed in IL-6 gene-disrupted mice as compared to wild-type animals. IL-6 was found to play a role in the initial differentiation of Th1 cells but not in their expansion. The defect found after IL-6 depletion or in IL-6-knockout mice was compensated by the inclusion of recombinant mouse IL-12 in the vaccine. The induction of protective immunity against an intravenous or an aerosol challenge with live, virulent M. tuberculosis was markedly reduced by neutralizing either IL-6 or IL-12 during immunization with the vaccine. Likewise, the effects of IL-6 neutralization were partially reversed by including IL-12 in the vaccine. Our data point to an important role of IL-6 and IL-12 in the generation of cell-mediated immunity to tuberculosis.
Leal
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IS
Laboratory of Microbiology, Institute for Molecular and Cell Biology, University of Porto, Porto, Portugal.
Smedegârd
B
B
Andersen
P
P
Appelberg
R
R
D000818:Animals; D001500:BCG Vaccine / Q000276:immunology*; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000502:physiology*; D015850:Interleukin-6 / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D000644:Quaternary Ammonium Compounds / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014611:Vaccination
D001500:BCG Vaccine; D015850:Interleukin-6; D000644:Quaternary Ammonium Compounds; D018664:Interleukin-12; C015831:dimethyldioctadecylammonium; D007371:Interferon-gamma