HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Akiba, H. Articles by Nicolas, J.-F. Search for Related Content PubMed PubMed Citation Articles by Akiba, H. Articles by Nicolas, J.-F. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB 1-FLUORO-2,4-DINITROBENZENE

Skin Inflammation During Contact Hypersensitivity Is Mediated by Early Recruitment of CD8⁺ T Cytotoxic 1 Cells Inducing Keratinocyte Apoptosis¹

Hitoshi Akiba^2,*,, Jeanne Kehren^3,*, Marie-Thérèse Ducluzeau^*, Maya Krasteva^*, Françoise Horand^*, Dominique Kaiserlian, Fumio Kaneko and Jean-François Nicolas^*

Institut National de la Santé et de la Recherche Médicale, ^* Unité 503 and Unité 404, Lyon, France; and Department of Dermatology, Fukushima Medical University School of Medicine, Fukushima, Japan

Contact hypersensitivity (CHS) is a T cell-mediated, Ag-specific skin inflammation induced by skin exposure to haptens in sensitized individuals. Th1/T cytotoxic 1 cells are effector cells of CHS, whereas Th2/T regulatory CD4⁺ T cells have down-regulating properties. We have previously shown that CHS to 2,4-dinitrofluorobenzene is mediated by specific CD8⁺ effector cells, whose cytolytic activity is mandatory for induction of skin inflammation. In this study, using immunohistochemistry and RT-PCR analysis, we show that CD8⁺ T cells are rapidly recruited into the skin at the site of hapten challenge before the onset of clinical and histological signs of skin inflammation. This early CD8⁺ T cell recruitment is concomitant with: 1) transient IFN- mRNA expression suggesting local activation of effector cells; and 2) induction of keratinocyte (KC) apoptosis which gradually increased to a maximum at the peak of the CHS response. Alternatively, skin infiltration of CD4⁺ T cells occurred later and coincided with the peak of the CHS reaction and the beginning of the resolution of skin inflammation. Mice deficient in CD8⁺ T cells did not develop CHS, whereas mice deficient in CD4⁺ T cells developed an enhanced inflammatory response with increased numbers of CD8⁺ T cells recruited in the skin associated with massive KC apoptosis. These data show that CHS is due to the early and selective recruitment in the skin of CD8⁺ T cytotoxic 1 effector cells responsible for KC apoptosis.

This article has been cited by other articles:

				S. Rana, S. N. Byrne, L. J. MacDonald, C. Y.-Y. Chan, and G. M. Halliday Ultraviolet B Suppresses Immunity by Inhibiting Effector and Memory T Cells Am. J. Pathol., April 1, 2008; 172(4): 993 - 1004. [Abstract] [Full Text] [PDF]

				R. Watanabe, M. Fujimoto, N. Ishiura, Y. Kuwano, H. Nakashima, N. Yazawa, H. Okochi, S. Sato, T. F. Tedder, and K. Tamaki CD19 Expression in B Cells Is Important for Suppression of Contact Hypersensitivity Am. J. Pathol., August 1, 2007; 171(2): 560 - 570. [Abstract] [Full Text] [PDF]

				D. D. Kish, A. V. Gorbachev, and R. L. Fairchild Regulatory function of CD4+CD25+ T cells from Class II MHC-deficient mice in contact hypersensitivity responses J. Leukoc. Biol., July 1, 2007; 82(1): 85 - 92. [Abstract] [Full Text] [PDF]

				A. Hennino, M. Vocanson, Y. Toussaint, K. Rodet, J. Benetiere, A.-M. Schmitt, M.-F. Aries, F. Berard, A. Rozieres, and J.-F. Nicolas Skin-Infiltrating CD8+ T Cells Initiate Atopic Dermatitis Lesions J. Immunol., May 1, 2007; 178(9): 5571 - 5577. [Abstract] [Full Text] [PDF]

				J. Kotner and R. Tarleton Endogenous CD4+ CD25+ Regulatory T Cells Have a Limited Role in the Control of Trypanosoma cruzi Infection in Mice Infect. Immun., February 1, 2007; 75(2): 861 - 869. [Abstract] [Full Text] [PDF]

				K. Viswanathan, C. Daugherty, and F. S. Dhabhar Stress as an endogenous adjuvant: augmentation of the immunization phase of cell-mediated immunity Int. Immunol., August 1, 2005; 17(8): 1059 - 1069. [Abstract] [Full Text] [PDF]

				E. Garaczi, M. Szell, T. Janossy, A. Koreck, A. Pivarcsi, E. Buzas, Z. Pos, A. Falus, A. Dobozy, and L. Kemeny Negative regulatory effect of histamine in DNFB-induced contact hypersensitivity Int. Immunol., December 1, 2004; 16(12): 1781 - 1788. [Abstract] [Full Text] [PDF]

				S. F. Martin, J. C. Dudda, V. Delattre, E. Bachtanian, C. Leicht, B. Burger, H. U. Weltzien, and J. C. Simon 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 J. Immunol., September 1, 2004; 173(5): 3178 - 3185. [Abstract] [Full Text] [PDF]

				A. Cavani, F. Nasorri, C. Ottaviani, S. Sebastiani, O. De Pita, and G. Girolomoni Human CD25+ Regulatory T Cells Maintain Immune Tolerance to Nickel in Healthy, Nonallergic Individuals J. Immunol., December 1, 2003; 171(11): 5760 - 5768. [Abstract] [Full Text] [PDF]

				B. Dubois, L. Chapat, A. Goubier, M. Papiernik, J.-F. Nicolas, and D. Kaiserlian Innate CD4+CD25+ regulatory T cells are required for oral tolerance and inhibition of CD8+ T cells mediating skin inflammation Blood, November 1, 2003; 102(9): 3295 - 3301. [Abstract] [Full Text] [PDF]

				P. Saint-Mezard, C. Chavagnac, S. Bosset, M. Ionescu, E. Peyron, D. Kaiserlian, J.-F. Nicolas, and F. Berard Psychological Stress Exerts an Adjuvant Effect on Skin Dendritic Cell Functions In Vivo J. Immunol., October 15, 2003; 171(8): 4073 - 4080. [Abstract] [Full Text] [PDF]