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CCR5 and CXCR4 chemokine receptor expression and beta-chemokine production during early T cell repopulation induced by highly active anti-retroviral therapy.
- Source :
-
Clinical and experimental immunology [Clin Exp Immunol] 1999 Oct; Vol. 118 (1), pp. 87-94. - Publication Year :
- 1999
-
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.
- Subjects :
- Adult
Anti-HIV Agents therapeutic use
Antigens, CD immunology
Antigens, CD metabolism
CD4-Positive T-Lymphocytes drug effects
CD4-Positive T-Lymphocytes immunology
CD4-Positive T-Lymphocytes metabolism
CD8-Positive T-Lymphocytes drug effects
CD8-Positive T-Lymphocytes immunology
CD8-Positive T-Lymphocytes metabolism
Chemokine CCL3
Chemokine CCL4
Chemokine CCL5 biosynthesis
Drug Therapy, Combination
Female
Flow Cytometry
HIV Infections drug therapy
HIV Infections immunology
Humans
Lectins pharmacology
Macrophage Inflammatory Proteins biosynthesis
Male
Middle Aged
T-Lymphocytes drug effects
T-Lymphocytes immunology
Time Factors
Viral Load
Chemokines, CC biosynthesis
HIV Infections metabolism
Receptors, CCR5 biosynthesis
Receptors, CXCR4 biosynthesis
T-Lymphocytes metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0009-9104
- Volume :
- 118
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Clinical and experimental immunology
- Publication Type :
- Academic Journal
- Accession number :
- 10540164
- Full Text :
- https://doi.org/10.1046/j.1365-2249.1999.01033.x