Development of effector CD8+ T cells in contact hypersensitivity occurs independently of CD4+ T cells

Abstract

Contact hypersensitivity (CHS) is a T cell-mediated response to hapten sensitization of the epidermis. Recent results from this laboratory indicated that hapten sensitization induces two populations of hapten-reactive T cells: CD8+ T cells producing IFN-gamma, which mediate the response, and CD4+ T cells producing IL-4 and IL-10, which function to limit the magnitude and the duration of the response. In the current report we first examined the hapten-presenting cell priming each of these T cell populations and then examined the influence of CD4+ T cell priming on the development of the CD8+ effector T cells. Isolation of hapten-presenting Langerhans cells from the lymph nodes of oxazolone-sensitized mice and transfer to naive mice resulted in the induction of both the regulatory CD4+ and the effector CD8+ T populations. Both CD4+ and CD8+ T cells expressing high levels of the activation determinants CD11a and CD44 appeared in the lymph nodes 3 days after hapten sensitization. The CD8+ T cells producing IFN-gamma and mediating CHS responses following transfer to naive mice were restricted to the high CD44-expressing population. In vitro activation of hapten-immune CD8+ T cells resulted in very low amounts (3 U/ml) of IL-2 production, whereas production of IL-2 by immune CD4+ T cells was approximately 70-fold higher (208 U/ml). Despite this discrepancy in IL-2 production and the coincidental priming of CD4+ and CD8+ T cells by hapten-presenting Langerhans cells during hapten sensitization, the numbers of CD8+/high CD44-expressing T cells in the lymph nodes were nearly identical when CD4+ T cells were present or absent during hapten priming. These results indicate that coincidental priming of CD4+ (and CD8+) T cells by LC does not augment CD8+ T cell development in CHS.