TNF-α Antagonism Generates a Population of Antigen-Specific CD4+CD25+ T Cells That Inhibit Protective Immunity in Murine Histoplasmosis

摘要: In both humans and mice, treatment with TNF-α antagonists is associated serious infectious complications including disseminated histoplasmosis. The mechanisms by which inhibition of endogenous alter protective immunity remain obscure. Herein, we tested the possibility that neutralization this cytokine triggered emergence T cells dampen immunity. lungs mice given mAb to contained a higher proportion number CD4+CD25+ than controls. This elevation was not observed in IFN-γ- or GM-CSF-deficient those high inoculum. Phenotypic analysis revealed these lacked many characteristics natural regulatory cells, Foxp3. from TNF-α-neutralized suppressed Ag-specific, but nonspecific, responses vitro. Elimination CD25+ vivo restored adoptive transfer inhibited vitro vivo, suppressive effect reversed IL-10. Thus, induction population an Ag-specific manner Histoplasma capsulatum.