Regulatory function of CD4+CD25+ T cells from Class II MHC-deficient mice in contact hypersensitivity responses

Danielle D. Kish^*^,1, Anton V. Gorbachev^* and Robert L. Fairchild^*^,^,

^* Department of Immunology and
Urological Institute, Cleveland Clinic Foundation, Cleveland, Ohio, USA; and
Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA

¹ Correspondence: NB3-30, Department of Immunology, Cleveland Clinic Foundation, 9500 Euclid Ave., Cleveland, OH 44195-0001, USA. E-mail: kishd{at}ccf.org

Contact hypersensitivity (CHS) is a CD8+ T cell-mediated, inflammatoryresponse to hapten sensitization and challenge of the skin.During sensitization, the magnitude and duration of hapten-specificCD8+ T cell expansion in the skin-draining lymph nodes (LN)are restricted by CD4+CD25+ T regulatory cells (Treg). The regulationof hapten-specific CD8+ T cell priming in Class II MHC-deficient(MHC–/–) mice was investigated. Although hapten-specificCD8+ T cell priming and CHS responses were elevated in ClassII MHC–/– versus wild-type mice, presensitizationdepletion of CD4+ or CD25+ cells in Class II MHC–/–mice further increased CD8+ T cell priming and the elicitedCHS response. Flow cytometry analyses of LN cells from ClassII MHC–/– mice revealed a population of CD4+ T cellswith a majority expressing CD25. Forkhead box p3 mRNA was expressedin LN cells from Class II MHC–/– and was reducedto background levels by depletion of CD4+ or CD25+ cells. IsolatedCD4+CD25+ T cells from wild-type and Class II MHC–/–mice limited in vitro proliferation of alloantigen- and hapten-specificT cells to antigen-presenting stimulator cells. These resultsidentify functional CD4+CD25+ Treg in Class II MHC–/–mice, which restrict hapten-specific CD8+ T cell priming andthe magnitude of CHS responses.

Key Words: suppression • Treg • MHC–/–