Interleukin-6 regulates the phenotype of the immune response to a tuberculosis subunit vaccine.
We investigated the role of interleukin-6 (IL-6) in the development of the immune response to a subunit vaccine against tuberculosis consisting of the culture filtrate proteins of Mycobacterium tuberculosis emulsified in the adjuvant dimethyldioctadecylammonium bromide (DDA). C57Bl/6 mice immunized with this vaccine developed a strong T helper 1 (Th1) response characterized by an increased production of interferon-gamma (IFN-gamma) secreted by CD4+ T cells. Neutralization of IL-6 during in vivo priming resulted in marked reduction in the ability of T cells to secrete IFN-gamma and IL-2 and to proliferate. IL-6 gene-disrupted mice primed with the vaccine showed a decrease in the number of IFN-gamma-producing cells and an increase in IL-4-secreting cells as compared to control mice. In contrast, neutralization of IL-6 during a boost of the vaccine in previously primed mice did not affect the development of IFN-gamma-producing cells but still increased the number of IL-4-producing cells. Our work shows that IL-6 plays a major role in the priming but not in the later expression of a Th1 response to a tuberculosis vaccine.
Leal
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IS
Laboratory of Microbiology and Immunology of Infection, Institute for Molecular and Cell Biology, University of Porto, Porto, Portugal.
Flórido
M
M
Andersen
P
P
Appelberg
R
R
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001500:BCG Vaccine / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018929:Cell Culture Techniques; D002455:Cell Division / Q000276:immunology; D005260:Female; D007117:Immunization, Secondary; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018417:Th1 Cells / Q000276:immunology*; D014611:Vaccination
D000911:Antibodies, Monoclonal; D001500:BCG Vaccine; D007376:Interleukin-2; D015850:Interleukin-6; D015847:Interleukin-4; D007371:Interferon-gamma