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

We report that interleukin (IL)-4 and IL-10 can significantly up- or down-r egulate CXC chemokine receptor 4 (CXCR4) expression on CD4(+) T lymphocytes , respectively. Stromal cell-derived factor-1 alpha (SDF-1 alpha)-induced C D4(+) T-lymphocyte chemotaxis was also correspondingly regulated by IL-4 an d 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 rever se transcription-polymerase chain reaction (RT-PCR). Scatchard analysis rev ealed a type of CXCR4 with affinity (K-d approximate to 6.3 nm), and approx imate 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-d 1 approximate to 4.4 nm and K-d2 approximate to 14.6 nm), and a total of ap proximate to 130 000 SDF-1 alpha-binding sites per cell, among IL-4-stimula ted CD4(+) T lymphocytes. The regulation of CXCR4 expression in CD4(+) T ly mphocytes by IL-4 and IL-10 could be blocked by a selective inhibitor of pr otein kinase (staurosporine) or by a selective inhibitor of cAMP- and cGMP- dependent protein kinase (H-8), indicating that these cytokines regulate CX CR4 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 expressi on 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 resu lts 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 envi ronment concerning the inflammatory processes and in the progression of hum an immunodeficiency virus (HIV) infection.