Abnormal expression of intracellular cytokines and chemokine receptors in peripheral blood T lymphocytes from patients with systemic sclerosis

Abstract

Summary 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-γ (IFN-γ), interleukin-2 (IL-2), IL-4, and IL-13, and chemokine receptors such as CXCR3 and CCR4 by flow cytometry. The frequency of IFN-γ-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-γ- 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-γ-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-γ, 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.