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 vari...

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Bibliographic Details
Published in:The Journal of immunology (1950) 2004-09, Vol.173 (5), p.3178-3185
Main Authors: Martin, Stefan F, Dudda, Jan C, Delattre, Virginie, Bachtanian, Eva, Leicht, Cornelia, Burger, Beate, Weltzien, Hans Ulrich, Simon, Jan C
Format: Article
Language:English
Subjects:
Animals
Apoptosis - immunology
CD4-Positive T-Lymphocytes - immunology
CD4-Positive T-Lymphocytes - physiology
CD8-Positive T-Lymphocytes - immunology
CD8-Positive T-Lymphocytes - physiology
Dermatitis, Contact - immunology
fas Receptor
Granzymes
Interferon-gamma - metabolism
Mice
Mice, Knockout
Proteins - genetics
Proteins - immunology
Proteins - physiology
Receptors, Tumor Necrosis Factor
Serine Endopeptidases - deficiency
Serine Endopeptidases - genetics
Trinitrobenzenes - immunology
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Summary: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.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.173.5.3178