| Title | CCR5 and CXCR4 chemokine receptor expression and beta-chemokine production during early T cell repopulation induced by highly active anti-retroviral therapy. | | Author(s) | Giovannetti A, Ensoli F, Mazzetta F, De Cristofaro M, Pierdominici M, Muratori DS, Fiorelli V, Aiuti F | | Institution | Department of Allergy and Clinical Immunology, University 'La Sapienza', Rome, Italy. | | Source | Clin Exp Immunol 1999 Oct; 118(1):87-94. | | MeSH | Adult
Anti-HIV Agents
Antigens, CD
CD4-Positive T-Lymphocytes
CD8-Positive T-Lymphocytes
Chemokines, CC
Drug Therapy, Combination
Female
Flow Cytometry
HIV Infections
Humans
Lectins
Macrophage Inflammatory Protein-1
Male
Middle Aged
RANTES
Receptors, CCR5
Receptors, CXCR4
Research Support, Non-U.S. Gov't
T-Lymphocytes
Time Factors
Viral Load
| | Abstract | Expression of chemokine receptors and beta-chemokine production by peripheral blood mononuclear cells (PBMC) were determined in HIV-1-infected individuals before and after highly active anti-retroviral therapy (HAART) and their relationship to viral load, T cell phenotype and the expression of immunological activation markers was examined. We found that the expression of CCR5 is up-regulated in HIV-1-infected individuals while CXCR4 appears down-regulated on both CD4 and CD8 T cells compared with normal controls. These alterations are associated with the high levels of viral load. In addition, a relationship was observed between the degree of immune activation and chemokine receptor expression on T cells. However, after 3 months of combined anti-retroviral regimen, expression of CXCR4 significantly increased while CCR5 decreased when compared with pretherapy determinations. This was seen in strict association with a dramatic decrease of viral load and an increase of both CD45RA+/CD62L+ (naive) and CD45RA-/CD62L+ or CD45RA+/CD62L- (memory) T cells accompanied by a significant decrease of the expression of immune activation markers such as HLA-DR and CD38. At enrolment, both spontaneous and lectin-induced RANTES, macrophage inflammatory protein-1alpha (MIP-1alpha) and MIP-1beta production by PBMC were higher in HIV-1-infected individuals compared with normal controls, although differences for MIP-1beta were not statistically significant. However, RANTES and MIP-1alpha production decreased during HAART at levels closer to that determined with normal controls, while MIP-1beta production was less consistently modified. These data indicate that the expression of chemokine receptors CCR5 and CXCR4 and the production of beta-chemokines are altered in HIV-infected individuals, and suggest that their early modifications during HAART reflect both the peripheral redistribution of naive/memory T cell compartments and the decrease in levels of T cell activation. Such modifications in the expression of host determinants of viral tropism and the production of anti-viral molecules may play a role in the emergence of virus variants when a failure of HAART occurs. | | Language | eng | | Pub Type(s) | Journal Article
| | PubMed ID | 10540164 |
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