The majority of epidermal T cells in Psoriasis vulgaris lesions can produce type 1 cytokines, interferon-gamma, interleukin-2, and tumor necrosis factor-alpha, defining TC1 (cytotoxic T lymphocyte) and TH1 effector populations: a type 1 differentiation bias is also measured in circulating blood T cells in psoriatic patients.
Psoriasis vulgaris is a skin disease potentially mediated by pro-inflammatory cytokines produced by type 1 lesional T cells. The capability of individual T cells to produce these cytokines in lesional skin is not known. In this study we measured the ability of lesional and peripheral blood T cells to produce intracellular interferon-gamma, tumor necrosis factor-alpha, interleukin-2, interleukin-4, and interleukin-10 proteins as detected by flow cytometric analysis. Cytokine synthesis was induced by activation with ionomycin/phorbol myristate acetate (in the presence of Brefeldin A, which inhibits the exocytosis of these cytokines). After stimulation, we found relatively high percentages of epidermal CD8 and CD4 T cells capable of producing interferon-gamma, tumor necrosis factor-alpha, and interleukin-2, whereas few T cells, < 11%, expressed interleukin-4 or interleukin-10. Hence both CD8+ and CD4+ T cells are capable of type 1 effector functions (TC1 and TH1, respectively). This activation scheme was repeated on peripheral blood T cells from psoriatic patients versus healthy controls, where we also found a type 1 bias. In order to evaluate quantitatively the type 1 cytokine bias, we compared the frequency of type 2 interleukin-4 producing versus type 1 interferon-gamma producing T cells in our assay and found a shift towards type 1 producing cells. This shift reveals a type 1 differentiation bias in both lesional areas and in the peripheral blood, which may indicate an imbalance within the T cell population, which is contributing to the chronic or sustained immunologic activation of T cells found in this disease.
Austin
L M
LM
laboratory of Investigative Dermatology, The Rockerfeller University, New York, New York 10021-6399, USA. austinl@rockvax.rockerfeller.edu
Ozawa
M
M
Kikuchi
T
T
Walters
I B
IB
Krueger
J G
JG
D000328:Adult; D000368:Aged; D016516:CD4-CD8 Ratio; D002454:Cell Differentiation / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis*; D000078404:Epidermal Cells; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000097:blood; D007376:Interleukin-2 / Q000096:biosynthesis / Q000097:blood; D015759:Ionomycin / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D011565:Psoriasis / Q000097:blood / Q000473:pathology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D013602:T-Lymphocytes, Cytotoxic / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D018417:Th1 Cells / Q000166:cytology / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D016207:Cytokines; D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D015759:Ionomycin; D007371:Interferon-gamma; D013755:Tetradecanoylphorbol Acetate