IL-4 and a glucocorticoid up-regulate CXCR4 expression on human CD4+ T lymphocytes and enhance HIV-1 replication.

CXCR4 is a key co-receptor required for the infection of T-tropic HIV-1 strain of CD4+ T lymphocytes. The regulation of this chemokine receptor was therefore studied. Th2 polarized cells expressed more CXCR4 than Th1 cells. Among a panel of cytokines and stimulants, a Th2 type cytokine interleukin-4 (IL-4) selectively up-regulated the mRNA level as well as surface protein expression of CXCR4 within 16 h. In addition, CXCR4 was also up-regulated by a glucocorticoid, dexamethasone. These treated cells became more responsive in transendothelial migration assays to the specific CXCR4 ligand, SDF-1alpha. Furthermore, up-regulation of CXCR4 was also associated with the enhancement of HIV replication in human CD4+ T lymphocytes. This study indicates the enhanced T-tropic HIV-1 infection to CD4+ T lymphocytes through up-regulation of CXCR4 by several immunomodulating agents, IL-4, and a glucocorticoid. These findings may explain the shift to T-tropic HIV-1 dominance during AIDS progression when Th2 comes to predominate.