Recruitment and differentiation of helper T-cell 22 cells in malignant ascites due to hepatic carcinoma

Objective To investigate the distribution and phenotypic characteristics of helper T-cell 22 (Th22) cells in malignant ascites (MA) and peripheral blood from hepatic carcinoma patients, and the mechanism by which Th22 cells differentiate and recruit into the peritoneal space. Methods To determine the distribution and phenotypic features of Th22 cells in MA and peripheral blood. Purified naive CD4+ T cells isolated from MA and peripheral blood were stimulated with cytokines. MA was used to stimulate chemotaxis of Th22 cells in the absence or presence of anti-chemokine ligand 20 (CCL20), anti-CCL22, or/and anti-CCL27 mAbs. Results Th22 cells in MA [(3.22±0.40)%, n=37) were obviously higher than peripheral blood [(0.79±0.20)%, n=37, P=0.006) from MA patients and healthy controls [(0.63±0.11)%, n=10, P=0.002], Th17 cells in MA [(3.30±0.18)%] were obviously higher than peripheral blood [(0.79±0.15)%, n=37, P=0.008] from MA patients and healthy controls [(0.67±0.12)%, n=10, P=0.001] Th22 cells correlated positively with Th17 cells in MA (P=0.001). Th22 cells expressed high levels of CD45RO, CC chemokine receptor (CCR) 4, CCR6 and CCR10, medium level of CCR7, and low levels of CD45RA, CD62L, CCR3 and CCR5 in MA. Th22 cells were facilitated by interleukin-6 (IL-6), IL-1b, and/or tumor necrosis factor-α (IFN-α), and inhibited by interferon-γ (IFN-γ) differentiate from CD4+ T cells. MA were chemotactic for Th22 cells, that could be interdicted by anti-CCL20, anti-CCL22, and anti-CCL27 mAbs. Conclusion Chemokines and cytokines may contribute to the increased Th22 cells in MA. Th22 cells probably participate in pathogenic mechanism of MA and may play an important role in immune regulation of human peritoneal malignant environment. Key words: Helper T-cell 22 cells; Hepatic carcinoma; Malignant ascites; Chemotaxis; Differentiation