Kinetics of the T-cell receptor CD4 and CD8 Vβ repertoire in HIV-1 vertically infected infants early treated with HAART

Maria Luisa Romiti, Caterina Cancrini, Guido Castelli-Gattinara, Silvia Di Cesare, Patrizia Ciaffi, Stefania Bernardi, Marco Rossi De Gasperi, Eva Halapi, Paolo Rossi

Research output: Contribution to journalArticlepeer-review

Abstract

Objectives: To determine the kinetics and the relationship between the T-cell receptor Vβ (TCRBV) complementary determining region 3 length, the CD4 T-cell count and HIV viral load changes in HIV-1 infected infants treated early with highly active antiretroviral therapy (HAART) during 1 year of follow-up. Design: Two HIV-1 vertically infected infants, two HIV-1 vertically exposed uninfected and two healthy controls were analysed by spectratyping. Evaluation of viral load, CD4 naive and memory cell counts and a proliferation test were also carried out. Methods: Twenty-six families and subfamilies of the TCR on CD4 and CD8 T cells were analyzed by spectratyping. Flow cytometric analysis on peripheral blood mononuclear cells for CD4CD45Ra, CD4CD45Ro, CD8CD38, proliferation tests and plasma viral load measurements were performed at baseline, 1, 6 and after 12 months of therapy. Results: HAART induced a marked reduction of viral load in both HIV-1 infected infants and an increase to normal CD4 T-cell count in the symptomatic infant. At baseline the TCRBV family distribution in the majority of CD8 and a few of the CD4 T cells was highly perturbed, with several TCRBV families showing a monoclonal/oligoclonal distribution. During HAART a normalization of the TCR repertoire in both CD8 and CD4 subsets occurred. TCR repertoire normalization was associated with a good virological and immunological response. Conclusion: These results suggest that complete and early virus replication control as a result of early HAART leads to a marked reduction of T-cell oligoclonality and is an essential prerequisite to the development of a polyclonal immune response in HIV-1 infected infants.

Original languageEnglish
Pages (from-to)2075-2084
Number of pages10
JournalAIDS (London, England)
Volume15
Issue number16
DOIs
Publication statusPublished - Nov 9 2001

Keywords

  • HAART
  • Immune reconstitution
  • Paediatrics
  • T-cell repertoire
  • Vertical HIV-1 infection

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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