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Herein, we tested the possibility that neutralization of this cytokine triggered the emergence of T cells that dampen immunity. The lungs of mice given mAb to TNF-\u03b1 contained a higher proportion and number of CD4+CD25+ cells than controls. This elevation was not observed in IFN-\u03b3- or GM-CSF-deficient mice or in those given a high inoculum. Phenotypic analysis revealed that these cells lacked many of the characteristics of natural regulatory T cells, including Foxp3. CD4+CD25+ cells from TNF-\u03b1-neutralized mice suppressed Ag-specific, but not nonspecific, responses in vitro. Elimination of CD25+ cells in vivo restored protective immunity in mice given mAb to TNF-\u03b1 and adoptive transfer of CD4+CD25+ cells inhibited immunity. In vitro and in vivo, the suppressive effect was reversed by mAb to IL-10. Thus, neutralization of TNF-\u03b1 is associated with the induction of a population of regulatory T cells that alter protective immunity in an Ag-specific manner to Histoplasma capsulatum.<\/jats:p>","DOI":"10.4049\/jimmunol.180.2.1088","type":"journal-article","created":{"date-parts":[[2014,4,18]],"date-time":"2014-04-18T19:09:13Z","timestamp":1397848153000},"page":"1088-1097","source":"Crossref","is-referenced-by-count":40,"title":["TNF-\u03b1 Antagonism Generates a Population of Antigen-Specific CD4+CD25+ T Cells That Inhibit Protective Immunity in Murine Histoplasmosis"],"prefix":"10.1093","volume":"180","author":[{"suffix":"Jr.","given":"George S","family":"Deepe","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases, Veterans Affairs Hospital, University of Cincinnati College of Medicine , Cincinnati, OH 45267"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reta S","family":"Gibbons","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Veterans Affairs Hospital, University of Cincinnati College of Medicine , Cincinnati, OH 45267"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2008,1,15]]},"reference":[{"key":"2025032610021099600_R1","first-page":"3012","volume-title":"Principles and Practices of Infectious Diseases","year":"2004"},{"key":"2025032610021099600_R2","first-page":"1163","volume-title":"N. 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