title: Skin homing (cutaneous lymphocyte-associated antigen-positive) CD8+ T cells respond to superantigen and contribute to eosinophilia and IgE production in atopic dermatitis.
abstract: In allergic inflammations of the skin, activation of CD4+ T cells was demonstrated to play an important role; however, a minor role for CD8+ T cells is implied. In the present study, we compared cutaneous lymphocyte-associated Ag (CLA)-expressing CD4+ and CD8+ subsets, which were isolated from peripheral blood and lesional skin biopsies in atopic dermatitis (AD) patients. We demonstrated that CD8+CLA+ T cells proliferate in response to superantigen and are as potent as CD4+CLA+ T cells in IgE induction and support of eosinophil survival. In atopic skin inflammation, the existence of high numbers of CD4+ and CD8+ T cells was demonstrated by immunohistochemistry and by culturing T cells from skin biopsies. In peripheral blood, both CD4+ and CD8+ subsets of CLA+CD45RO+ T cells were in an activated state in AD. The in vivo-activated CLA+ T cells of both subsets spontaneously released an IL-5- and IL-13-dominated Th2 type cytokine pattern. This was confirmed by intracytoplasmic cytokine staining immediately after isolation of the cells from peripheral blood. In consequence, both CD4+ and CD8+, CLA+ memory/effector T cells induced IgE production by B cells mainly by IL-13, and enhanced eosinophil survival in vitro by delaying eosinophil apoptosis, mainly by IL-5. These results indicate that in addition to the CD4+ subset, the CD8+CLA+ memory/effector T cells are capable of responding to superantigenic stimulation and play an important role in the pathogenesis of AD.
authors.affiliation: Swiss Institute of Allergy and Asthma Research (SIAF), Davos, Switzerland. akdism@siaf.unizh.ch
authors.forename: M
authors.initials: M
authors.lastname: Akdis
authors.forename: H U
authors.initials: HU
authors.lastname: Simon
authors.forename: L
authors.initials: L
authors.lastname: Weigl
authors.forename: O
authors.initials: O
authors.lastname: Kreyden
authors.forename: K
authors.initials: K
authors.lastname: Blaser
authors.forename: C A
authors.initials: CA
authors.lastname: Akdis
mesh_terms: D000328:Adult; D000945:Antigens, Differentiation, T-Lymphocyte; D000951:Antigens, Neoplasm; D017209:Apoptosis / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002470:Cell Survival / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D003876:Dermatitis, Atopic / Q000276:immunology* / Q000473:pathology; D004768:Enterotoxins / Q000276:immunology; D004802:Eosinophilia / Q000276:immunology* / Q000473:pathology; D005260:Female; D006801:Humans; D007073:Immunoglobulin E / Q000096:biosynthesis*; D007156:Immunologic Memory; D018793:Interleukin-13 / Q000096:biosynthesis / Q000502:physiology; D015848:Interleukin-5 / Q000096:biosynthesis; D017493:Leukocyte Common Antigens / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000097:blood; D016201:Receptors, Lymphocyte Homing / Q000096:biosynthesis / Q000097:blood; D012867:Skin / Q000276:immunology* / Q000473:pathology; D013211:Staphylococcus aureus / Q000276:immunology; D018089:Superantigens / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000378:metabolism
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; D000951:Antigens, Neoplasm; C063419:CTAGE1 protein, human; D016207:Cytokines; D004768:Enterotoxins; D018793:Interleukin-13; D015848:Interleukin-5; D008562:Membrane Glycoproteins; D016201:Receptors, Lymphocyte Homing; D018089:Superantigens; D007073:Immunoglobulin E; C031818:enterotoxin B, staphylococcal; D017493:Leukocyte Common Antigens