Neutrophil Expression of FasL and Perforin Directs Effector CD8 T Cell Infiltration into Antigen Challenged Skin1
| Autor: | Kish, Danielle D., Gorbachev, Anton V., Parameswaran, Neetha, Gupta, Neetu, Fairchild, Robert L. |
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| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Mice
Knockout Pore Forming Cytotoxic Proteins Fas Ligand Protein integumentary system Neutrophils hemic and immune systems chemical and pharmacologic phenomena CD8-Positive T-Lymphocytes Dermatitis Contact Article Mice Inbred C57BL Disease Models Animal Mice Gene Expression Regulation Cell Movement Animals Dinitrofluorobenzene Female Antigens Ear External Skin |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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