Abnormal expression of intracellular cytokines and chemokine receptors in peripheral blood T lymphocytes from patients with systemic sclerosis.
In patients with systemic sclerosis (SSc), there are conflicting findings regarding which is predominant between type 1 and type 2 immune responses. To determine the balance between type 1 and type 2 T lymphocytes in peripheral blood from SSc patients, we investigated the expression of intracellular cytokines, such as interferon-gamma (IFN-gamma), interleukin-2 (IL-2), IL-4, and IL-13, and chemokine receptors such as CXCR3 and CCR4 by flow cytometry. The frequency of IFN-gamma-producing cells among CD8+ cells was significantly increased in patients with diffuse cutaneous SSc (n = 11, P < 0.0001) and limited cutaneous SSc (lSSc; n= 16, P < 0.0001) compared with normal controls (n = 17) while there was no significant difference in the frequency of IL-4- or IL-13-producing cells. In contrast, the frequency of IFN-gamma- or IL-4-producing cells among CD4+ cells was similar between the three groups. Similar results were obtained when absolute numbers were assessed. The frequency of IFN-gamma-producing cells among CD8+ cells inversely correlated with percentage DLco in SSc patients (r = - 0.650, P < 0.005). CXCR3+ CD8+ cells selectively produced IFN-gamma, and the frequency of CXCR3+ CD45RO+ cells among CD8+ cells was higher in lSSc patients (n = 14, P < 0.01) than in normal controls (n = 22). In contrast, there was no significant difference in the frequencies of CXCR3- or CCR4-expressing CD45RO+ cells among CD4+ cells. These results demonstrate the predominance of type 1 cytokine-producing cells (Tc1 cells) in peripheral blood CD8+ T cells from SSc patients, but no definite Th1/Th2 imbalance in CD4+ T cells. Tc1 cells may be associated with pulmonary vascular damage in SSc.
Fujii
H
H
Department of Dermatology, Cancer Research Institute, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.
Hasegawa
M
M
Takehara
K
K
Mukaida
N
N
Sato
S
S
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000032:analysis; D016022:Case-Control Studies; D016207:Cytokines / Q000032:analysis*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007371:Interferon-gamma / Q000097:blood; D018793:Interleukin-13 / Q000032:analysis; D007376:Interleukin-2 / Q000032:analysis; D015847:Interleukin-4 / Q000032:analysis; D007424:Intracellular Fluid / Q000276:immunology; D008297:Male; D008875:Middle Aged; D054398:Receptors, CCR4; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000032:analysis*; D012595:Scleroderma, Systemic / Q000276:immunology*; D018709:Statistics, Nonparametric; D013601:T-Lymphocytes / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D015415:Biomarkers; C515354:CCR4 protein, human; C515187:CXCR3 protein, human; D016207:Cytokines; D018793:Interleukin-13; D007376:Interleukin-2; D054398:Receptors, CCR4; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine; D015847:Interleukin-4; D007371:Interferon-gamma