title: Neutrophil expression of Fas ligand and perforin directs effector CD8 T cell infiltration into antigen-challenged skin.
abstract: Contact hypersensitivity (CHS) is a T cell response to hapten skin challenge of sensitized individuals proposed to be mediated by hapten-primed CD8 cytolytic T cells. Effector CD8 T cell recruitment into hapten challenge sites to elicit CHS requires prior CXCL1- and CXCL2-mediated neutrophil infiltration into the site. We investigated whether neutrophil activities directing hapten-primed CD8 T cell skin infiltration in response to 2,4-dinitro-1-fluorobenzene (DNFB) required Fas ligand (FasL) and perforin expression. Although DNFB sensitization of gld/perforin-/- mice induced hapten-specific CD8 T cells producing IFN-γ and IL-17, these T cells did not infiltrate the DNFB challenge site to elicit CHS but did infiltrate the challenge site and elicit CHS when transferred to hapten-challenged naive wild-type recipients. Hapten-primed wild-type CD8 T cells, however, did not elicit CHS when transferred to naive gld/perforin-/- recipients. Wild-type bone marrow neutrophils expressed FasL and perforin, and when transferred to sensitized gld/perforin-/- mice, they restored hapten-primed CD8 T cell infiltration into the challenge site and CHS. The FasL/perforin-mediated activity of wild-type neutrophils induced the expression of T cell chemoattractants, CCL1, CCL2, and CCL5, within the hapten-challenged skin. These results indicate FasL/perforin-independent functions of hapten-primed CD8 T cells in CHS and identify new functions for neutrophils in regulating effector CD8 T cell recruitment and immune responses in the skin.
authors: Department of Immunology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA. kishd@ccf.org
authors: Danielle D
authors: DD
authors: Kish
authors: Anton V
authors: AV
authors: Gorbachev
authors: Neetha
authors: N
authors: Parameswaran
authors: Neetu
authors: N
authors: Gupta
authors: Robert L
authors: RL
authors: Fairchild
mesh_terms: D000818:Animals; D000941:Antigens / Q000008:administration & dosage; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D002465:Cell Movement / Q000235:genetics / Q000276:immunology*; D003877:Dermatitis, Contact / Q000276:immunology* / Q000473:pathology; D004139:Dinitrofluorobenzene / Q000008:administration & dosage* / Q000276:immunology; D004195:Disease Models, Animal; D004431:Ear, External; D053222:Fas Ligand Protein / Q000096:biosynthesis / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism; D052899:Pore Forming Cytotoxic Proteins / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics*; D012867:Skin / Q000276:immunology*
chemical_list: D000941:Antigens; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D052899:Pore Forming Cytotoxic Proteins; C483886:perforin, mouse; D004139:Dinitrofluorobenzene