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

被引:83
|
作者
Chen, X
Winkler-Pickett, RT
Carbonetti, NH
Ortaldo, JR
Oppenheim, JJ
Howard, OMZ
机构
[1] NCI, Basic Res Program, SAIC Frederick Inc, Mol Immunoregulat Lab, Frederick, MD 21702 USA
[2] NCI, Expt Immunol Lab, Ctr Canc Res, Frederick, MD 21702 USA
[3] Univ Maryland, Sch Med, Dept Microbiol & Immunol, Baltimore, MD 21201 USA
[4] NCI, Mol Immunoregulat Lab, Ctr Canc Res, Frederick, MD 21702 USA
关键词
CD4(+)CD25(+) T regulatory cells; experimental autoimmune encephalomyelitis; pertussis toxin;
D O I
10.1002/eji.200535353
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
We observed a remarkable reduction in the frequency and immunosuppressive activity of splenic CD4(+)CD25(+) T cells in C57BL/6 mice with MOG(33-55)-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.
引用
收藏
页码:671 / 680
页数:10
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