Distinct functions of CXCR3+ and CCR4+CD4+ T-cells accumulated in human tuberculosis pleural fluid

BACKGROUND: Chemokine receptors and their ligands play a prominent role in regulating leucocyte migration. In the local milieu of inflammation, a high concentration of chemokines can recruit different chemokine receptor-expressing lymphocytes. OBJECTIVE: To understand the distinct immunological functions of CXC chemokine receptor 3 (CXCR3+) and CC chemokine receptor 4 (CCR4+) cluster of differentiation 4 (CD4+) T-cells accumulated in human tuberculosis (TB) pleural fluid after tuberculous antigen stimulation. METHODS: Mononuclear cells were isolated from the peripheral blood of healthy donors, cord blood and TB pleural fluid, and expression of CXCR3 and CC chemokine receptor 4 (CCR4), cytokines and cytolytic molecules by CD4+ T-cells with or without stimulation were analysed using fluorescence-activated cell sorting. RESULTS: CXCR3 and CCR4 expression on CD4+ T-cells from pleural fluid mononuclear cells (PFMCs) was significantly higher than in peripheral blood mononuclear cells (PBMCs). T-cell receptor signalling resulted in the upregulation of CXCR3 and CCR4 expression on CD4+ T-cells from cord blood mononuclear cells (CBMCs) and PBMCs in a time-dependent manner, but not from PFMCs. After stimulation with Mycobacterium tuberculosis antigens, CXCR3+CCR4-CD4+ T-cells were dominated by multifunctional T-helper 1 cells; however, CXCR3+CCR4+CD4+ T-cells exhibited cytotoxicity and degranulation by expressing granzyme B, perforin, CD107a/b and tumour necrosis factor-related apoptosis-inducing ligand. CONCLUSION: Our results indicated that CXCR3 or CCR4 expression on CD4+ T-cells had different biological activities against tuberculous infection, and could be a potential marker for the diagnosis of TB.