TNF-alpha antagonism generates a population of antigen-specific CD4+CD25+ T cells that inhibit protective immunity in murine histoplasmosis

The Journal of Immunology : Official Journal of the American Association of Immunologists
George S Deepe, Reta S Gibbons

Abstract

In both humans and mice, treatment with TNF-alpha antagonists is associated with serious infectious complications including disseminated histoplasmosis. The mechanisms by which inhibition of endogenous TNF-alpha alter protective immunity remain obscure. 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-alpha contained a higher proportion and number of CD4+CD25+ cells than controls. This elevation was not observed in IFN-gamma- 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-alpha-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-alpha 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-alpha is associated with the induction of a population of regulatory T cells that alter protective immunity in an Ag-specific manner to Histop...Continue Reading

References

Apr 7, 1998·Infection and Immunity·J A Cain, G S Deepe
Oct 19, 2000·The New England Journal of Medicine·A P LimayeW E Stamm
Feb 13, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·P ZhouR A Seder
Mar 13, 2001·Annual Review of Immunology·M Feldmann, R N Maini
Mar 13, 2001·Annual Review of Immunology·K W MooreA O'Garra
Oct 13, 2001·The New England Journal of Medicine·J KeaneM M Braun
Sep 11, 2002·Proceedings of the National Academy of Sciences of the United States of America·Ava J WuHugh O McDevitt
Nov 27, 2002·Proceedings of the National Academy of Sciences of the United States of America·Wanda NiedbalaFoo Y Liew
Mar 4, 2003·Nature Immunology·Jason D FontenotAlexander Y Rudensky
Mar 5, 2003·American Journal of Respiratory and Critical Care Medicine·Karen L WoodHomer L Twigg
Aug 29, 2003·Expert Opinion on Biological Therapy·Yasmine Belkaid
Nov 11, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·George S Deepe, Reta S Gibbons
Feb 10, 2004·European Journal of Immunology·Hans-Willi Mittrücker, Stefan H E Kaufmann
Feb 24, 2004·Infection and Immunity·Alexandra I MedeirosLúcia H Faccioli
May 6, 2004·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·R S WallisD O Beenhouwer
Jul 29, 2004·The Journal of Experimental Medicine·Michael R EhrensteinClaudia Mauri
Aug 6, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Barry T Rouse, Susmit Suvas
Sep 3, 2004·Nature Reviews. Immunology·Thomas R Malek, Allison L Bayer
Oct 16, 2004·Immunity·Ching-Tai HuangDario A A Vignali
Mar 23, 2005·Immunity·Jason D FontenotAlexander Y Rudensky
Mar 24, 2005·Nature Immunology·Harald von Boehmer
Mar 24, 2005·Nature Immunology·Yasmine Belkaid, Barry T Rouse
Apr 6, 2005·The Journal of Experimental Medicine·Julien C MarieAlexander Y Rudensky
Apr 23, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Isabelle SuffiaYasmine Belkaid
Apr 27, 2005·Seminars in Arthritis and Rheumatism·Paul J Anderson
Apr 27, 2005·Seminars in Arthritis and Rheumatism·Joachim Sieper, Jan Van Den Brande
May 10, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jr-Shiuan LinBetty A Wu-Hsieh
Dec 20, 2005·The Journal of Infectious Diseases·George S Deepe, Reta S Gibbons
Jan 21, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Claudia MontagnoliLuigina Romani
Mar 11, 2006·Trends in Immunology·Kathryn J Wood, Birgit Sawitzki
Mar 15, 2006·The Journal of Experimental Medicine·Isabelle J SuffiaYasmine Belkaid
Mar 16, 2006·Blood·Xavier ValenciaPeter E Lipsky
Aug 22, 2006·Nature·Li-Fan LuRandolph J Noelle

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Citations

Aug 1, 2013·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Sima S ToussiThomas J Walsh
Jan 30, 2015·Expert Opinion on Drug Safety·Giuseppe MurdacaFrancesco Puppo
Sep 27, 2008·Current Rheumatology Reports·Sujata Sarkar, David A Fox
Apr 12, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Danielle N Kroetz, George S Deepe
Dec 5, 2009·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·D IshiiR L Fairchild
Jan 25, 2012·The Journal of Infectious Diseases·Danielle N Kroetz, George S Deepe
Jun 11, 2015·Future Microbiology·Michael C HorwathGeorge S Deepe
Jul 29, 2016·The Journal of Immunology : Official Journal of the American Association of Immunologists·Mariam Mathew GeorgeGeorge S Deepe
Jan 31, 2009·Medical Mycology·Luigina Romani
Jan 10, 2012·Annual Review of Immunology·Marcel WüthrichBruce Klein
Jun 11, 2020·Biomolecules·Morgana K B PradoLúcia H Faccioli
Jul 17, 2009·International Journal of Antimicrobial Agents·Roberto NicoleteLúcia H Faccioli

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