DEFECTIVE INNATE IMMUNITY UNDERLIES THE ABSENCE OF CONTACT SENSITIVITY RESPONSES IN gld/perforin−/− MICE

Contact hypersensitivity (CHS) is a CD8 T cell mediated immune response to sensitization and challenge of the skin. Hapten‐primed CD8T cell recruitment into hapten challenge sites requires prior CXCL1/KC‐mediated neutrophil infiltration. Although primed CD8 T cells do not express cytolytic activity, CHS is absent in gld /perforin −/− mice. CD8 T cell priming to sensitization with 2, 4‐dinitrofluorobenzene (DNFB) and T cell and neutrophil infiltration into DNFB challenged skin in gld /perforin −/− mice vs. wild‐type C57BL/6 (WT) mice were tested. ELISPOT analyses indicated equivalent priming of DNFB‐specific CD8 cells in WT and gld /perforin −/− mice. DNFB‐primed CD8 T cells from WT or gld /perforin −/− mice transferred equivalent CHS responses to naïve WT recipients. Production of KC was equivalent in challenged skin of DNFB sensitized WT and gld /perforin −/− mice. However, there was little/no neutrophil infiltration into the challenge site of sensitized gld /perforin −/− mice. CHS responses were restored in gld /perforin −/− mice when WT neutrophils were injected into the challenge site just before hapten challenge. These results indicate that Fas L and perforin are required for the initial neutrophil infiltration into hapten challenge sites that induce subsequent effector CD8 T cell recruitment to mediate CHS responses.