Nickel-responding T cells are CD4+ CLA+ CD45RO+ and express chemokine receptors CXCR3, CCR4 and CCR10.
BACKGROUND
Whereas T lymphocytes are widely accepted as effector cells determining the pathogenesis of allergic contact dermatitis, contradictory results have been found regarding the roles of different T-cell subsets. The use of various experimental models, involving long-term cultured T-cell lines or clones, may explain these contradictory results.


OBJECTIVE
To investigate the involvement of distinct T-cell subsets in patients with nickel contact allergy.


METHODS
Different T-cell subsets were directly isolated from peripheral blood mononuclear cells (PBMCs) of nickel-allergic patients, and their proliferative capacity, type-1 or type-2 cytokine secretion [measured by interferon (IFN)-gamma or interleukin (IL)-5 release] and phenotypical marker expression were analysed after stimulation with nickel.


RESULTS
Only CD4+ CLA+ CD45RO+ and not CD8+ T cells proliferate and produce both type-1 (IFN-gamma) and type-2 (IL-5) cytokines in response to nickel. Moreover, cells expressing the marker CLA in combination with CD4, CD45RO or CD69 are increased after nickel-specific stimulation. Interestingly, in addition, CD45RA+ CLA+ cells showed an increased frequency after allergen-specific stimulation. Analysis of nickel-reactive T cells for expression of distinct chemokine receptors showed that both proliferative capacity and cytokine production are restricted to subsets expressing CXCR3, CCR4 but not CCR6. Fluorescence-activated cell sorting analysis of chemokine receptors expressed on nickel-stimulated T cells confirmed these results; a subset of T cells expressing CLA and CXCR3, CCR4 and, most importantly, CCR10 increased in response to allergen, while these CLA+ nickel-reactive T cells were all negative for CCR6.


CONCLUSIONS
These findings demonstrate that freshly isolated nickel-reactive T cells can be characterized as CD4+ CLA+ memory T cells which express the chemokine receptors CXCR3, CCR4 and CCR10, but not CCR6.
Department of Dermatology, VU University Medical Centre, PO Box 7057, 1007 MB Amsterdam, The Netherlands.
H
H
Moed
D M
DM
Boorsma
T J
TJ
Stoof
B M E
BM
von Blomberg
D P
DP
Bruynzeel
R J
RJ
Scheper
S
S
Gibbs
T
T
Rustemeyer
D015703:Antigens, CD / Q000032:analysis*; D000945:Antigens, Differentiation, T-Lymphocyte; D000951:Antigens, Neoplasm; D015704:CD4 Antigens / Q000032:analysis; D016022:Case-Control Studies; D017449:Dermatitis, Allergic Contact / Q000276:immunology*; D003875:Drug Eruptions / Q000276:immunology*; D005434:Flow Cytometry; D006801:Humans; D007156:Immunologic Memory; D017493:Leukocyte Common Antigens / Q000032:analysis; D008562:Membrane Glycoproteins / Q000032:analysis; D009532:Nickel / Q000009:adverse effects*; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D054447:Receptors, CCR10; D054398:Receptors, CCR4; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000032:analysis*; D018709:Statistics, Nonparametric; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D000951:Antigens, Neoplasm; C515706:CCR10 protein, human; C515354:CCR4 protein, human; D015704:CD4 Antigens; C063419:CTAGE1 protein, human; C515187:CXCR3 protein, human; D008562:Membrane Glycoproteins; D054447:Receptors, CCR10; D054398:Receptors, CCR4; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine; D009532:Nickel; D017493:Leukocyte Common Antigens; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1