Enhanced murine contact hypersensitivity by depletion of endogenous regulatory T cells in the sensitization phase

Abstract

Regulatory T cells (Treg) play essential roles in the regulation of immune responses [ [1] Sakaguchi S. Yamaguchi T. Nomura T. Ono M Regulatory T cells and immune tolerance. Cell. 2008; 133: 775-787 Abstract Full Text Full Text PDF PubMed Scopus (3614) Google Scholar ]. Contact hypersensitivity (CHS) is a prototype of T-cell mediated delayed-type hypersensitivity reactions [ [2] Grabbe S. Schwarz T. Immunoregulatory mechanisms involved in elicitation of allergic contact hypersensitivity. Immunol Today. 1998; 19: 37-44 Abstract Full Text PDF PubMed Scopus (474) Google Scholar ], mainly mediated by interferon (IFN)-γ producing type 1 helper T cells and cytotoxic T cells [ [3] Mori T. Kabashima K. Yoshiki R. Sugita K. Shiraishi N. Onoue A. et al. Cutaneous hypersensitivities to hapten are controlled by IFN-gamma-upregulated keratinocyte Th1 chemokines and IFN-gamma-downregulated langerhans cell Th2 chemokines. J Invest Dermatol. 2008; 128: 1719-1727 Crossref PubMed Scopus (67) Google Scholar ]. Transfer of exogenous Treg during the elicitation phase is known to suppress CHS in IL-10 [ [4] Ring S. Schafer S.C. Mahnke K. Lehr H.A. Enk A.H. CD4+ CD25+ regulatory T cells suppress contact hypersensitivity reactions by blocking influx of effector T cells into inflamed tissue. Eur J Immunol. 2006; 36: 2981-2992 Crossref PubMed Scopus (103) Google Scholar ] and CD39 dependent manners [ [5] Ring S. Oliver S.J. Cronstein B.N. Enk A.H. Mahnke K. CD4+ CD25+ regulatory T cells suppress contact hypersensitivity reactions through a CD39, adenosine-dependent mechanism. J Allergy Clin Immunol. 2009; 123 (e1282): 1287-1296 Abstract Full Text Full Text PDF PubMed Scopus (85) Google Scholar ]. However, Foxp3, a master transcriptional factor and thus far the only reliable marker for Treg, exists intracellularly, hampering ex vivo isolation or in vivo depletion of endogenous Treg. Therefore, it remains largely unclear whether endogenous Treg mediate such suppressive roles in vivo.