CXC chemokine receptor 4 expression and stromal cell-derived factor-1 alpha-induced chemotaxis in CD4(+) T lymphocytes are regulated by interleukin-4 andinterleukin-10

We report that interleukin (IL)-4 and IL-10 can significantly up- or down-regulate CXC chemokine receptor 4 (CXCR4) expression on CD4(+) T lymphocytes, respectively. Stromal cell-derived factor-1 alpha (SDF-1 alpha)-induced CD4(+) T-lymphocyte chemotaxis was also correspondingly regulated by IL-4 and IL-10. IL-4 and IL-10 up- or down-regulated CXCR4 mRNA expression in CD4(+) T lymphocytes, respectively, as detected by real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR). Scatchard analysis revealed a type of CXCR4 with affinity (K-d approximate to 6.3 nm), and approximate to 70 000 SDF-1 alpha-binding sites per cell, among freshly isolated CD4(+) T lymphocytes, and two types of CXCR4 with different affinities (K-d1 approximate to 4.4 nm and K-d2 approximate to 14.6 nm), and a total of approximate to 130 000 SDF-1 alpha-binding sites per cell, among IL-4-stimulated CD4(+) T lymphocytes. The regulation of CXCR4 expression in CD4(+) T lymphocytes by IL-4 and IL-10 could be blocked by a selective inhibitor of protein kinase (staurosporine) or by a selective inhibitor of cAMP- and cGMP-dependent protein kinase (H-8), indicating that these cytokines regulate CXCR4 on CD4(+) T lymphocytes via both cAMP and cGMP signalling pathways. The fact that cyclosporin A or ionomycin were able to independently change the CXCR4 expression and block the effects of IL-4 and IL-10 on CXCR4 expression implied that the capacity of IL-4 and IL-10 to regulate CXCR4 on CD4(+) T lymphocytes is not linked to calcium-mobilization stimulation. These results indicate that the effects of IL-4 and IL-10 on the CXCR4-SDF-1 receptor-ligand pair may be of particular importance in the cytokine/chemokine environment concerning the inflammatory processes and in the progression of human immunodeficiency virus (HIV) infection.