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.
Wang
J
J
Department of Molecular Preventive Medicine, School of Medicine and CREST, University of Tokyo, Japan.
Harada
A
A
Matsushita
S
S
Matsumi
S
S
Zhang
Y
Y
Shioda
T
T
Nagai
Y
Y
Matsushima
K
K
D000276:Adjuvants, Immunologic / Q000009:adverse effects / Q000494:pharmacology*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism / Q000821:virology*; D002478:Cells, Cultured; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology*; D019718:Receptors, CXCR4 / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D013268:Stimulation, Chemical; D018417:Th1 Cells / Q000187:drug effects / Q000378:metabolism / Q000821:virology; D018418:Th2 Cells / Q000187:drug effects / Q000378:metabolism / Q000821:virology; D014158:Transcription, Genetic; D015854:Up-Regulation / Q000187:drug effects*; D014779:Virus Replication / Q000187:drug effects*
D000276:Adjuvants, Immunologic; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D007166:Immunosuppressive Agents; D019718:Receptors, CXCR4; D015847:Interleukin-4; D003907:Dexamethasone