CXC Chemokine Receptor 4 Expression On CD4～+T Lymphocytes Are Regulated By Interleukin-4 And Interleukin-10

We have observed a novel phenomenon that IL-4 can significantly up-or down-regulate CXCR4 expression on CD4~T lymphocytes, respectively.SDF-1-induced CD4~T lymphocyte chemotaxis is also regulated by IL-4 and IL- 10, correspondingly. IL-4 and IL- 10 up-or down-regulate CXCR4 mRNA expression in CD4~T lymphocytes, respectively, using real time quantitative RT-PCR.Scatchard analysis reveals a kind of CXCR4 with affinity (Kd 6.3 nM) on freshly isolated CD4~T lymphocytes, and two kinds of CXCR4 with different affinities (KdI 4.4 nM and Kd2 14.6 nM) on IL-4stimulated CD4~T lymphocytes. The regulation of CXCR4 expression in CD4~T lymphocytes by IL-4 and IL- 10 can be blocked by a selective inhibitor of protein kinase (staurosporine) or 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 signaling pathways. The facts that cyclosporin A or ionomycin can independently change the CXCR4 expression and block the effects of IL-4 and IL- 10 on CXCR4 expression imply that capacity of IL-4 and IL- 10 to regulate CXCR4 on CD4~T lymphocytes is not linked to calcium-mobilization stimulation. We have also found that IL-4 and IL- 10 may be via CD26 molecule to regulate CXCR4 expression on CD4~T lymphocytes. These results indicate that the effects of IL-4 and IL- 10 on CXCR4-SDF1 receptor-ligand pair may be especially important in cytokine/chemokine environment concerning the inflammatory processes and the progression of HIV infection.