CD4+CD25+ regulatory T cells utilize FasL as a mechanism to restrict DC priming functions in cutaneous immune responses.
Recent studies have suggested Fas-mediated elimination of antigen-presenting cells as an important mechanism down-regulating the induction of autoimmune responses. It remains unknown whether this mechanism restricts the magnitude of immune responses to non-self antigens. We used a mouse model of a cutaneous CD8(+) T-cell-mediated immune response (contact hypersensitivity, CHS) to test if CD4(+)CD25(+) T cells expressing FasL regulate hapten-specific effector CD8(+) T cell expansion through the elimination of Fas-expressing hapten-presenting DC. In WT mice, attenuation of CD4(+)CD25(+) T regulatory cell activity by anti-CD25 mAb increased hapten-presenting DC numbers in skin-draining LN, which led to increased effector CD8(+) T-cell priming for CHS responses. In contrast, CD4(+)CD25(+) T cells did not regulate hapten-specific CD8(+) T-cell priming and CHS responses initiated by Fas-defective (lpr) DC. Thus, restricting DC priming functions through Fas-FasL interactions is a potent mechanism employed by CD4(+)CD25(+) regulatory cells to restrict CD8(+) T-cell-mediated allergic immune responses in the skin.
Gorbachev
Anton V
AV
Department of Immunology, Cleveland Clinic Foundation, Cleveland, OH, USA. gorbaca@ccf.org
Fairchild
Robert L
RL
D019264:Adoptive Transfer; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D015704:CD4 Antigens / Q000096:biosynthesis; D049109:Cell Proliferation; D002478:Cells, Cultured; D003877:Dermatitis, Contact / Q000235:genetics / Q000276:immunology*; D053222:Fas Ligand Protein / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D005260:Female; D006241:Haptens / Q000008:administration & dosage; D053645:Interleukin-2 Receptor alpha Subunit / Q000096:biosynthesis; D007801:Langerhans Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D019463:Mice, Inbred MRL lpr; D009154:Mutation / Q000235:genetics; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
D015704:CD4 Antigens; D053222:Fas Ligand Protein; D006241:Haptens; D053645:Interleukin-2 Receptor alpha Subunit
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