Protective and memory immunity to Histoplasma capsulatum in the absence of IL-10.
We determined whether the absence of IL-10 in mice influenced protective and memory immunity to Histoplasma capsulatum. IL-10(-/-) mice cleared primary and secondary infection more rapidly than wild-type controls. Administration of mAb to TNF-alpha or IFN-gamma, but not GM-CSF, abrogated protection in naive IL-10(-/-) mice; mAb to TNF-alpha, but not IFN-gamma or GM-CSF, subverted protective immunity in secondary histoplasmosis. The inflammatory cell composition in IL-10(-/-) mice was altered in those given mAb to IFN-gamma or TNF-alpha. More Gr-1(+) and Mac-3(+) cells were present in lungs of IL-10(-/-) mice given mAb to IFN-gamma, and treatment with mAb to TNF-alpha sharply reduced the number of CD8(+) cells in lungs of IL-10(-/-) mice. We ascertained whether the lack of IL-10 modulated memory T cell generation or the protective function of cells. The percentage of CD3(+), CD44(high), CD62(low), and IFN-gamma(+) cells in IL-10(-/-) mice was higher than that of wild-type at day 7 but not day 21 or 49 after immunization. Fewer splenocytes from immunized IL-10(-/-) mice were required to mediate protection upon adoptive transfer into infected TCR alphabeta(-/-) mice. Hence, deficiency of IL-10 confers a salutary effect on the course of histoplasmosis, and the beneficial effects of IL-10 deficiency require endogenous TNF-alpha and/or IFN-gamma. Memory cell generation was transiently increased in IL-10(-/-) mice, but the protective function conferred by cells from these mice following immunization is strikingly more vigorous than that of wild-type.
Deepe
George S
GS
Veterans Affairs Hospital and Division of Infectious Diseases, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA. george.deepe@uc.edu
Gibbons
Reta S
RS
D019264:Adoptive Transfer; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D006658:Histoplasma / Q000254:growth & development / Q000276:immunology*; D006660:Histoplasmosis / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D007113:Immunity, Innate / Q000235:genetics; D007117:Immunization, Secondary; D007156:Immunologic Memory / Q000235:genetics; D007274:Injections, Intraperitoneal; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology; D016753:Interleukin-10 / Q000172:deficiency* / Q000235:genetics*; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D008172:Lung Diseases, Fungal / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008819:Mice, Nude; D009924:Organ Culture Techniques; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000637:transplantation; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology
D000911:Antibodies, Monoclonal; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma