Dichotomy of blood- and skin-derived IL-4-producing allergen-specific T cells and restricted V beta repertoire in nickel-mediated contact dermatitis.
In this study we compared the phenotype and cytokine patterns of nickel-specific T cell clones (TCC) derived from blood samples and positive patch test reactions. A total of 252 nickel-specific TCC were established from three nonatopic patients with allergic contact dermatitis caused by nickel. All TCC expressed the TCR-alpha beta, and 77% were CD4+ compared with 21% CD8+ TCC. In contrast to blood-derived TCC, the majority of skin-derived CD4+ or CD8+ T lymphocytes produced IL-4 either in combination with IFN-gamma (type 0 cytokine pattern) or IL-4 exclusively (type 2 pattern). Skin-derived nickel-specific TCC of each patient secreted significantly more IL-4 than blood-derived TCC of the same individual. Analysis of TCR-V beta repertoire from two patients indicated that >40% of the tested TCC expressed one of the following V beta elements: V beta 13.1/13.2, V beta 20, V beta 2, V beta 6.7, or V beta 14. Only 20% of unstimulated T cells but >40% of nickel-stimulated T cells derived from peripheral blood of the same individuals expressed these V beta elements, suggesting a selection of certain TCR-V beta elements by nickel sulfate in these patients. In contrast to the compartmentalization of IL-4 production, there were no major differences in the expression of TCR-V beta elements between blood- and skin-derived nickel-specific TCC. These results point to a modulation of the cytokine production pattern of T lymphocytes after their migration from peripheral blood into the skin and a production of the type 2 cytokine IL-4 in acute eczematous lesions in nonatopic individuals.
Werfel
T
T
Department of Dermatology, Hannover Medical School, Germany.
Hentschel
M
M
Kapp
A
A
Renz
H
H
D000485:Allergens / Q000097:blood* / Q000276:immunology; D002999:Clone Cells; D017449:Dermatitis, Allergic Contact / Q000097:blood* / Q000276:immunology*; D000939:Epitopes / Q000097:blood* / Q000276:immunology; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis / Q000097:blood*; D008213:Lymphocyte Activation / Q000187:drug effects; D005810:Multigene Family / Q000276:immunology; D009532:Nickel / Q000009:adverse effects* / Q000276:immunology / Q000494:pharmacology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis / Q000235:genetics*; D012867:Skin / Q000276:immunology* / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism
D000485:Allergens; D000939:Epitopes; D016693:Receptors, Antigen, T-Cell, alpha-beta; D015847:Interleukin-4; C029938:nickel sulfate; D009532:Nickel; D007371:Interferon-gamma