CD8 T cells producing IL-17 and IFN-gamma initiate the innate immune response required for responses to antigen skin challenge.
Effector CD8 T cell recruitment into the skin in response to Ag challenge requires prior CXCL1/KC-directed neutrophil infiltration. Mechanisms inducing CXCL1 production and the dynamics of neutrophil-CD8 T cell interactions during elicitation of Ag-specific responses in the skin were investigated. CXCL1 and CXCL2/MIP-2 were produced within 3-6 h of Ag challenge at 10-fold higher levels in skin challenge sites of Ag-sensitized vs nonsensitized mice. In the challenge sites of sensitized mice this production decreased at 6-9 h postchallenge to near the levels observed in skin challenge sites of nonsensitized mice but rose to a second peak 12 h after challenge. The elevated early neutrophil chemoattractant production at 3-6 h after skin challenge of sensitized animals required both IFN-gamma and IL-17, produced by distinct populations of Ag-primed CD8 T cells in response to Ag challenge. Although induced by the Ag-primed CD8 T cells, the early CXCL1 and CXCL2 production was accompanied by neutrophil but not CD8 T cell infiltration into the skin Ag challenge site. Infiltration of the CD8 T cells into the challenge site was not observed until 18-24 h after challenge. These results demonstrate an intricate series of early interactions between Ag-specific and innate immune components that regulate the sequential infiltration of neutrophils and then effector T cells into the skin to mediate an immune response.
Department of Immunology, Cleveland Clinic Foundation, Cleveland, OH 44195, USA. kishd@ccf.org
Danielle D
DD
Kish
Xiaoxia
X
Li
Robert L
RL
Fairchild
D019264:Adoptive Transfer; D000818:Animals; D000941:Antigens / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D054360:Chemokine CXCL1 / Q000096:biosynthesis / Q000276:immunology; D054426:Chemokine CXCL2 / Q000096:biosynthesis / Q000276:immunology; D003877:Dermatitis, Contact / Q000276:immunology* / Q000378:metabolism; D004139:Dinitrofluorobenzene / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D007113:Immunity, Innate; D007118:Immunoassay; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000276:immunology; D020381:Interleukin-17 / Q000096:biosynthesis* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D020556:Neutrophil Infiltration / Q000276:immunology; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000276:immunology; D012882:Skin Tests
D000941:Antigens; D054360:Chemokine CXCL1; D054426:Chemokine CXCL2; D020381:Interleukin-17; D007371:Interferon-gamma; D004139:Dinitrofluorobenzene