CCR5 and CXCR4 chemokine receptor expression and β-chemokine production during early T cell repopulation induced by highly active anti-retroviral therapy

A. Giovannetti, F. Ensoli, F. Mazzetta, M. De Cristofaro, M. Pierdominici, D. S. Muratori, V. Fiorelli, F. Aiuti

Research output: Contribution to journalArticlepeer-review

Abstract

Expression of chemokine receptors and β-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 upregulated in HIV-l-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 vital 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-1 α (MIP-1α) and MIP-1β production by PBMC were higher in HIV-1-infected individuals compared with normal controls, although differences for MIP-1 β were not statistically significant. However, RANTES and MIP-1 α production decreased during HAART at levels closer to that determined with normal controls, while MIP-1β production was less consistently modified. These data indicate that the expression of chemokine receptors CCR5 and CXCR4 and the production of β-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 level s 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.

Original languageEnglish
Pages (from-to)87-94
Number of pages8
JournalClinical and Experimental Immunology
Volume118
Issue number1
DOIs
Publication statusPublished - 1999

Keywords

  • Chemokine receptors
  • HIV HAART
  • β-chemokines

ASJC Scopus subject areas

  • Immunology

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