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Cytotoxicity is mandatory for CD8(+) T cell-mediated contact hypersensitivity
J Kehren1, C Desvignes, M Krasteva
1Institut National de la Santé et de la Recherche Médicale (INSERM) U503, Faculté Laennec, F-69372 Lyon Cedex 08, France.
The Journal of Experimental Medicine
|March 2, 1999
Summary
Cytotoxic CD8(+) T cells mediate contact hypersensitivity (CHS) skin inflammation. This T cell-mediated response requires either the perforin or Fas/Fas ligand pathway for cytotoxic activity, highlighting a role in harmful immune reactions.
Area of Science:
- Immunology
- Dermatology
- Cellular Biology
Background:
- Contact hypersensitivity (CHS) is a T cell-mediated skin inflammation.
- Previous studies identified major histocompatibility complex (MHC) class I-restricted CD8(+) T cells as mediators of CHS.
- The precise mechanism of CD8(+) T cell involvement in CHS remained to be fully elucidated.
Purpose of the Study:
- To investigate the role of cytotoxic activity of CD8(+) T cells in mediating CHS.
- To determine the specific cytotoxic pathways involved in CHS.
Main Methods:
- Utilized genetically modified mice deficient in perforin and/or Fas/Fas ligand (FasL) pathways.
- Examined CHS reactions in vivo and in vitro.
- Assessed the generation of hapten-specific cytotoxic T lymphocytes (CTLs).
Main Results:
- Mice deficient in both perforin and FasL failed to develop CHS and lacked hapten-specific CTLs, confirming the dependence on cytotoxic activity.
- Fas-deficient, FasL-deficient, and perforin-deficient mice exhibited normal CHS reactions and generated hapten-specific CTLs.
- In vitro studies confirmed that MHC class I-restricted CD8(+) T cells mediate CHS via either the perforin or Fas/FasL pathway.
Conclusions:
- Cytotoxic CD8(+) T cells are essential for mediating CHS skin inflammation.
- The CHS reaction relies on the cytotoxic function of CD8(+) T cells, utilizing either the perforin or Fas/FasL pathway.
- Cytotoxic CD8(+) T cells, typically involved in anti-tumor and anti-viral immunity, can also drive detrimental delayed-type hypersensitivity reactions.