T-cell re-population in HIV-infected children on highly active anti-retroviral therapy (HAART).
In this pilot study, we address the nature of the re-population of the T-cell compartment in HIV-1+ (Human Immunodeficiency Virus 1), vertically infected children placed on successful regimens of HAART (highly active anti-retroviral therapy) incorporating 2 NRTI and a protease inhibitor. The clonality of the T-cell compartment and the abundance of RTEs (Recent Thymic Emigrants) were determined 2 weeks before and 20 weeks after initiation of HAART in a subgroup of children taking part in the PENTA (Paediatric European Network for the Treatment of AIDS) 5 trial. Analysis of the clonality of the circulating T-cell compartment was assessed using CDR3 spectratyping and analysed using the Kolmogorov-Smirnov two sample test. This revealed that a high degree of T-cell clonal restriction still exists 5 months into therapy, despite the appearance of previously undetectable T-cell clones within the periphery. We detected no increase in RTE abundance in this 5 month period, as determined by PCR detection of TRECs (T-Cell Receptor Excision Circles). We conclude that the observed re-population of T cells within the periphery of treated children is heavily reliant upon the maintenance/expansion of pre-existing cells during the 5 month period immediately following the initiation of therapy.
King
D J
DJ
Department of Immunology, Imperial College School of Medicine at Chelsea & Westminster Hospital, London, UK. d.king@ic.ac.uk
Gotch
F M
FM
Larsson-Sciard
E L
EL
D000293:Adolescent; D023241:Antiretroviral Therapy, Highly Active; D002648:Child; D002675:Child, Preschool; D002986:Clinical Trials as Topic; D022801:Complementarity Determining Regions; D019674:Genes, T-Cell Receptor beta; D015658:HIV Infections / Q000276:immunology* / Q000635:transmission; D006801:Humans; D018445:Infectious Disease Transmission, Vertical; D018655:Lymphocyte Count; D010865:Pilot Projects; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
D022801:Complementarity Determining Regions