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 (ISSc; 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 ISSc 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.