Interferon-gamma inhibits the efficacy of interleukin 1 to generate a Th2-cell biased immune response induced by Leishmania major.
Splenic adherent cells from L. major-infected resistant and susceptible mice were restimulated in vitro and analyzed for the expression of IL-1 activity. Three weeks or later after infection, cells from parasite infected susceptible BALB/c mice produced substantially more IL-1 activity than those from non-infected controls or from L. major-infected resistant C57BL/6 animals. More than 95% of the IL-1 bioactivity was mediated by IL-1 alpha, as determined by blocking experiments with an anti-IL-1 alpha antiserum. The strain-specific differences in IL-1 production correlated with different accumulation of IL-1 producing adherent cells in the spleens of infected animals, but also with different IL-1 producing capacity on a per cell basis. When adherent cells were mixed with syngeneic IFN-gamma producing CD4+ T lymphocytes from L. major-infected C57BL mice or from animals that had been pretreated with anti-CD4 monoclonal antibody prior to infection, the level of detectable IL-1 decreased depending on the number of T cells added. This inhibition could be blocked completely with an anti-IFN-gamma antibody. No such effect was seen, when CD4+ cells were used that were derived from parasite-infected BALB/c mice and did not produce IFN-gamma. In contrast to L. major, L. donovani antigen not only failed to induce IL-1 production, but also dose-dependently suppressed the IL-1 activity elaborated by L. major antigen. We conclude from these data that IFN-gamma effectively inhibits the efficacy to IL-1 to generate to Th2-cell biased immune response induced by L. major. A T cell independent and as yet unknown mechanism to inhibit the IL-1 response is used by L. donovani.
Institut für Klinische Mikrobiologie, Universität Erlangen, Germany.
H M
HM
Wagner
H U
HU
Beuscher
M
M
Röllinghoff
W
W
Solbach
D000818:Animals; D000953:Antigens, Protozoan; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D006224:Cricetinae; D005260:Female; D007104:Immune Adherence Reaction; D007371:Interferon-gamma / Q000096:biosynthesis / Q000494:pharmacology; D007375:Interleukin-1 / Q000096:biosynthesis*; D007893:Leishmania donovani / Q000502:physiology; D007895:Leishmania tropica / Q000254:growth & development / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D013045:Species Specificity; D013154:Spleen / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
D000953:Antigens, Protozoan; D007375:Interleukin-1; D007371:Interferon-gamma