Expression and functional activity of CXCR-4 and CCR-5 chemokine receptors in human thymocytes.
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.
Zamarchi
R
R
Department of Oncology and Surgical Sciences, University of Padova, Italy.
Allavena
P
P
Borsetti
A
A
Stievano
L
L
Tosello
V
V
Marcato
N
N
Esposito
G
G
Roni
V
V
Paganin
C
C
Bianchi
G
G
Titti
F
F
Verani
P
P
Gerosa
G
G
Amadori
A
A
D015152:Blotting, Northern; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000494:pharmacology; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000494:pharmacology; D002675:Child, Preschool; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D015699:HIV Envelope Protein gp120 / Q000378:metabolism; D015497:HIV-1 / Q000145:classification / Q000502:physiology; D006801:Humans; D016130:Immunophenotyping; D007223:Infant; D007231:Infant, Newborn; D017136:Ion Transport / Q000187:drug effects; D008213:Lymphocyte Activation; D019402:Macrophage Inflammatory Proteins / Q000494:pharmacology; D008297:Male; D019713:Receptors, CCR5 / Q000096:biosynthesis* / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D019718:Receptors, CXCR4 / Q000096:biosynthesis* / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D015728:Receptors, HIV / Q000096:biosynthesis* / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology
C515255:CXCL12 protein, human; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D015699:HIV Envelope Protein gp120; D019402:Macrophage Inflammatory Proteins; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D015728:Receptors, HIV; D002118:Calcium