Defective neutrophil function underlies the absence of T cell recruitment into challenge sites during elicitation of contact sensitivity in gld/perforin-/- mice (60.7)

Abstract

Abstract Contact hypersensitivity (CHS) is a CD8 T cell mediated response to hapten sensitization and challenge of the skin. Hapten-primed CD8 T cell infiltration into the skin challenge site is not observed until 12-16 h post-challenge and requires prior neutrophil infiltration and activation within the site. The neutrophil activities required to direct this T cell infiltration to mediate CHS responses are undefined. Although primed CD8 T cells do not express FasL or perforin, CHS responses to 2, 4-dinitrofluorobenzene (DNFB) are absent in gld/perforin-/- mice. ELISPOT analyses indicated equivalent priming of DNFB-specific CD8 cells in sensitized wild-type (WT) and gld/perforin-/- mice. Whereas DNFB-primed CD8 T cells from WT or gld/perforin-/-mice transferred CHS responses to naïve WT recipients, WT CD8 T cells did not transfer the response to gld/perforin-/- mice. Neutrophil infiltration into the challenge site of sensitized gld/perforin-/- and WT mice was equivalent at 6 h post-challenge but T cell infiltration was absent in the challenge site of gld/perforin-/- mice at 18 h. This T cell infiltration and the CHS response were restored by transferring WT neutrophils i.v. to sensitized gld/perforin-/- mice at challenge. Neutrophils from sensitized WT mice expressed high levels of FasL and perforin mRNA. These results indicate that neutrophil expression of FasL and perforin required to direct effector CD8 T cell recruitment into the skin challenge site to mediate CHS responses.