IngentaConnect Expression and functional activity of CXCR-4 and CCR-5 chemokine ...

Authors: ZAMARCHI, R.¹; ALLAVENA, P.²; BORSETTI, A.³; STIEVANO, L.¹; TOSELLO, V.¹; MARCATO, N.¹; ESPOSITO, G.¹; RONI, V.¹; PAGANIN, C.²; BIANCHI, G.²; TITTI, F.³; VERANI, P.³; GEROSA, G.⁴; AMADORI, A.¹

Source: Clinical & Experimental Immunology, Volume 127, Number 2, February 2002 , pp. 321-330(10)

Publisher: Blackwell Publishing

Abstract:

SUMMARY

In this paper we addressed the expression of the HIV co-receptors CXCR-4 and CCR-5 in human thymocytes by phenotypic, molecular and functional approaches. Cytofluorimetric analysis disclosed that CXCR-4 was constitutively expressed by freshly isolated thymocytes (~10 000 molecules/cell in about 30% of thymocytes); the receptor was endowed with functional activity, as it mediated polarization, migration and intracellular Ca²⁺ increase in response to its ligand, SDF-1. On the contrary, CCR-5 expression in freshly isolated thymocytes was significantly lower (<4000 molecules/cell in less than 5% of the cells), and no functional response to CCR-5 agonists could be documented. Northern blot analysis of freshly isolated thymocytes showed high CXCR-4 mRNA levels, whereas the message for CCR-5 was barely detectable. On the other hand, a modest increase in the expression of CCR-5 was associated with in vitro thymocyte stimulation, and CCR-5 density at the cell surface attained CXCR-4 figures in most cases. None the less, no functional response to CCR-5 agonists could be documented in in vitro stimulated thymocytes. In vitro infection of thymocytes by CAT-expressing recombinant HIV bearing the envelope glycoproteins from different isolates showed that T-tropic strains, which use CXCR-4 as a co-receptor, were more efficient in infecting thymocytes than M-tropic strains, which preferentially use CCR-5. Altogether, these data indicate that expression of the major co-receptors involved in infection by M-tropic HIV strains is very poor in human thymocytes, and would suggest that thymocyte infection by M-tropic HIV strains may be a rare event in vivo.

Keywords: CXCR-4; CCR-5; HIV; thymus

Document Type: Research article

DOI: 10.1046/j.1365-2249.2002.01775.x

Affiliations: 1: Department of Oncology and Surgical Sciences, University of Padova, 2: Department of Immunology and Cell Biology, `Mario Negri' Institute, Milan, 3: Istituto Superiore di Sanità, Rome, and 4: Institute of Cardiovascular Surgery, University of Padova, Italy

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Expression and functional activity of CXCR-4 and CCR-5 chemokine receptors in human thymocytes