A high frequency of allergen-specific CD8+ Tc1 cells is associated with the murine immune response to the contact sensitizer trinitrophenyl.

Chemical haptens induce a variety of allergic immune reactions by induction of hapten-specific T cells. Contact sensitizers such as the hapten trinitrochlorobenzene (TNCB) elicit an allergic response, which is confined to the area of antigen exposure. Despite this localized allergic response, we show here that the trinitrophenyl (TNP)-specific immune response is characterized by a rapid induction of CD8+ Tc1 type cytotoxic effector cells already after a single allergen contact which can be detected in all secondary lymphoid organs tested. We furthermore demonstrate that the rapid induction of CD8+ Tc1 effector cells correlates with an unusually high frequency of polyclonal TNP-specific CD8+ effector T cells with specificities for a variety of MHC class I binding TNP-peptides carrying the hapten in different positions. These data suggest that allergies to chemical haptens may in part be due to an unusually high frequency of polyclonal, allergen-specific effector cells which are detected in all secondary lymphoid organs.

Fas-mediated inhibition of CD4+ T cell priming results in dominance of type 1 CD8+ T cells in the immune response to the contact sensitizer trinitrophenyl.

One of the unusual properties of chemically reactive haptens is their capacity to simultaneously generate immunogenic determinants for hapten-specific CD8(+) and CD4(+) T cells. Surprisingly, however, a clear dominance of CD8(+) effector T cells is observed in murine contact hypersensitivity to various haptens and upon T cell priming with hapten-modified APCs in vitro. In this study we show that trinitrophenyl-specific CD8(+) T cells actively prevent CD4(+) T cell priming in vitro. This process requires cell-cell contact and is dependent on the expression of Fas on the CD4(+) T cells. Our results reveal an important Fas-dependent mechanism for the regulation of hapten-specific CD4(+) T cell responses by CD8(+) T cells, which causes the dominance of CD8(+) effector T cells and the active suppression of a CD4(+) T cell response. Moreover, our demonstration of reduced contact hypersensitivity to trinitrophenyl in the absence of Fas, but not of perforin and/or granzymes A and B, underlines the important role of Fas as a pathogenetic factor for contact hypersensitivity.