HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Secchiero, P. Articles by Zauli, G. Search for Related Content PubMed PubMed Citation Articles by Secchiero, P. Articles by Zauli, G.

Engagement of CD28 Modulates CXC Chemokine Receptor 4 Surface Expression in Both Resting and CD3-Stimulated CD4⁺ T Cells¹

Paola Secchiero^2,3,*,, Davide Zella^2,*, Sabrina Curreli^*, Prisco Mirandola^*,, Silvano Capitani, Robert C. Gallo^* and Giorgio Zauli

^* Institute of Human Virology, University of Maryland, Baltimore, MD 21201; Department of Morphology and Embryology, Human Anatomy Section, University of Ferrara, Ferrara, Italy; and Institute of Normal Human Morphology, G. D’Annunzio University of Chieti, Chieti Scalo, Chieti, Italy

Optimal CD4⁺ T cell activation requires the cooperation of multiple signaling pathways coupled to the TCR-CD3 complex and to the CD28 costimulatory molecule. In this study, we have investigated the expression of surface CXC chemokine receptor 4 (CXCR4) in enriched populations of CD4⁺ T PBL, stimulated with anti-CD3 and anti-CD28 mAbs, immobilized on plastic. Anti-CD3 alone induced a progressive down-regulation of surface CXCR4, accompanied by a significant decline in the entry of the HXB2 T cell line-tropic (X4-tropic) HIV-1 clone in CD4⁺ T cells. Of note, this effect was strictly dependent on the presence in culture of CD14⁺ monocytes. On the other hand, anti-CD28 alone induced a small but reproducible increase in the expression of surface CXCR4 as well as in the entry of HXB2 HIV-1 clone in resting CD4⁺ T cells. When the two mAbs were used in combination, anti-CD28 potently synergized with anti-CD3 in inducing the expression of CD69 activation marker and stimulating the proliferation of CD4⁺ T cells. On the other hand, anti-CD28 counteracted the CXCR4 down-modulation induced by anti-CD3. The latter effect was particularly evident when anti-CD28 was associated to suboptimal concentrations of anti-CD3. Because CXCR4 is the major coreceptor for the highly cytopathic X4-tropic HIV-1 strains, which preferentially replicate in proliferating CD4⁺ T cells, the ability of anti-CD28 to up-regulate the surface expression of CXCR4 in both resting and activated CD4⁺ T cells provides one relevant mechanism for the progression of HIV-1 disease.