Pertussis toxin as an adjuvant suppresses the number and function of CD4<sup>+</sup>CD25<sup>+</sup> T regulatory cells

European Journal of Immunology - Tập 36 Số 3 - Trang 671-680 - 2006
Xin Chen1, Robin Winkler-Pickett2, Nicholas H. Carbonetti3, John R. Ortaldo2, Joost J. Oppenheim4, O. M. Zack Howard4
1Basic Research Program, SAIC-Frederick, Inc., Laboratory of Molecular Immunoregulation, National Cancer Institute-Frederick. Frederick, MD, USA
2Laboratory of Experimental Immunology , Center for Cancer Research, National Cancer Institute‐Frederick, Frederick, MD, USA
3Department of Microbiology and Immunology, University of Maryland, Medical School, Baltimore, MD, USA
4Laboratory of Molecular Immunoregulation, Center for Cancer Research, National Cancer Institute-Frederick, Frederick, MD, USA

Tóm tắt

AbstractWe observed a remarkable reduction in the frequency and immunosuppressive activity of splenic CD4+CD25+ T cells in C57BL/6 mice with MOG33–55‐induced experimental autoimmune encephalomyelitis (EAE). Our study revealed that pertussis toxin (PTx), one component of the immunogen used to induce murine EAE, was responsible for down‐regulating splenic CD4+CD25+ cells. Treatment of normal BALB/c mice with PTx in vivo reduced the frequency, suppressive activity and FoxP3 expression by splenic CD4+CD25+ T cells. However, PTx treatment did not alter the expression of characteristic phenotypic markers (CD45RB, CD103, GITR and CTLA‐4) and did not increase the expression of CD44 and CD69 by the residual splenic and lymph node CD4+CD25+ T cells. This property of PTx was attributable to its ADP‐ribosyltransferase activity. PTx did not inhibit suppressive activity of purified CD4+CD25+ T regulatory (Treg) cells in vitro, but did so in vivo, presumably due to an indirect effect. Although the exact molecular target of PTx that reduces Treg activity remains to be defined, our data suggests that alteration of both distribution and function of splenic immunocytes should play a role. This study concludes that an underlying cause for the immunological adjuvanticity of PTx is down‐regulation of Treg cell number and function.

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European Journal of Immunology

Tập 36 Số 3

671-680

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