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 Blood, 26 February 2009, Vol. 113, No. 9, pp. 1938-1947.
Prepublished online as a Blood First Edition Paper on December 8, 2008; DOI 10.1182/blood-2008-02-141275.

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IMMUNOBIOLOGY

CD4-CCR5 interaction in intracellular compartments contributes to receptor expression at the cell surface

Lamia Achour1,2, Mark G. H. Scott1,2, Hamasseh Shirvani1,2, Alain Thuret1,2, Georges Bismuth1,2, Catherine Labbé-Jullié1,2, and Stefano Marullo1,2

1 Institut Cochin, Université Paris Descartes, Centre National de la Recherche Scientifique (Unité Mixte de Recherche [UMR] 8104), Paris; and 2 Inserm U567, Paris, France

The association of CD4, a glycoprotein involved in T-cell development and antigen recognition, and CC chemokine receptor 5 (CCR5), a chemotactic G protein–coupled receptor, which regulates trafficking and effector functions of immune cells, forms the main receptor for HIV. We observed that the majority of CCR5 is maintained within the intracellular compartments of primary T lymphocytes and in a monocytic cell line, contrasting with its relatively low density at the cell surface. The CCR5-CD4 association, which occurs in the endoplasmic reticulum, enhanced CCR5 export to the plasma membrane in a concentration-dependent manner, whereas inhibition of endogenous CD4 with small interfering RNAs decreased cell-surface expression of endogenous CCR5. This effect was specific for CCR5, as CD4 did not affect cellular distribution of CXCR4, the other HIV coreceptor. These results reveal a previously unappreciated role of CD4, which contributes to regulating CCR5 export to the plasma membrane.


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