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.
Martin
Stefan F
SF
Clinical Research Group Allergology, Department of Dermatology, University of Freiburg, Germany. martin@haut.ukl.uni-freiburg.de
Dudda
Jan C
JC
Delattre
Virginie
V
Bachtanian
Eva
E
Leicht
Cornelia
C
Burger
Beate
B
Weltzien
Hans Ulrich
HU
Simon
Jan C
JC
D000818:Animals; D017209:Apoptosis / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000502:physiology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000502:physiology; D003877:Dermatitis, Contact / Q000276:immunology; D053804:Granzymes; D007371:Interferon-gamma / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D011506:Proteins / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D018124:Receptors, Tumor Necrosis Factor; D012697:Serine Endopeptidases / Q000172:deficiency / Q000235:genetics; D014301:Trinitrobenzenes / Q000276:immunology*; D019014:fas Receptor
C491899:Fas protein, mouse; D011506:Proteins; D018124:Receptors, Tumor Necrosis Factor; D014301:Trinitrobenzenes; D019014:fas Receptor; D007371:Interferon-gamma; D053804:Granzymes; C509214:Gzmb protein, mouse; D012697:Serine Endopeptidases