Pertussis toxin as an adjuvant suppresses the number and function of CD4+CD25+ T regulatory cells.
We 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.
Basic Research Program, SAIC-Frederick, Inc., Laboratory of Molecular Immunoregulation, National Cancer Institute-Frederick. Frederick, MD 21702-1201, USA. xinc@mail.ncifcrf.gov
Xin
X
Chen
Robin T
RT
Winkler-Pickett
Nicholas H
NH
Carbonetti
John R
JR
Ortaldo
Joost J
JJ
Oppenheim
O M Zack
OM
Howard
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000502:physiology*; D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D000943:Antigens, Differentiation / Q000276:immunology; D060908:CTLA-4 Antigen; D015536:Down-Regulation / Q000187:drug effects / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000276:immunology*; D005260:Female; D051858:Forkhead Transcription Factors / Q000276:immunology; D053450:Glucocorticoid-Induced TNFR-Related Protein; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D037342:Pertussis Toxin / Q000008:administration & dosage / Q000276:immunology*; D017475:Receptors, Nerve Growth Factor / Q000276:immunology; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology; D013154:Spleen / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D000276:Adjuvants, Immunologic; D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556707:Ctla4 protein, mouse; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D053450:Glucocorticoid-Induced TNFR-Related Protein; D017475:Receptors, Nerve Growth Factor; D018124:Receptors, Tumor Necrosis Factor; C106544:Tnfrsf18 protein, mouse; D037342:Pertussis Toxin