title: Diversity of the T-cell receptor BV repertoire in HIV-1-infected patients reflects the biphasic CD4+ T-cell repopulation kinetics during highly active antiretroviral therapy.
abstract: OBJECTIVE
  Highly active antiretroviral therapy (HAART) induces a decline in viral load and a biphasic increase in peripheral blood CD4+ T-cell counts in HIV-infected patients. To evaluate the effect of HAART on T-cell receptor (TCR) diversity of repopulating naive and memory CD4+ T cells, complementarity determining region 3 (CDR3) spectratyping was performed.
  
  
  METHODS
  For four patients treated with HAART, CD45RO+ (memory) and CD45RA+ (naive) CD4+ T cells were isolated from peripheral blood leukocyte samples obtained 1 week before, 1-2 months after, and 9-11 months after start of treatment.
  
  
  METHODS
  CDR3 regions were amplified by TCR-BV-specific nested PCR from CD4+ T-cell subsets. CDR3 size distributions and single-strand conformation polymorphism profiles were compared as an indication for TCR diversity.
  
  
  RESULTS
  Increasing blood CD4+ T-cell counts during the first 2 months of treatment coincided with increased perturbation of CDR3 patterns in CD4+ T-cell subsets, suggesting an early oligoclonal repopulation. At later timepoints, CDR3 size diversity increased when T-cell counts did not substantially decrease. Memory and naive CD4+ T cells generally showed comparable levels of perturbation.
  
  
  CONCLUSIONS
  Diversity of the TCR repertoire reflected biphasic T-cell repopulation during HAART, compatible with initial redistribution and later CD4+ T-cell production. Sustained elevation of T-cell counts will in principle result in restoration of TCR diversity.
authors.affiliation: Department of Clinical Viro-Immunology, CLB Sanquin Blood Supply Foundation and Laboratory for Clinical and Experimental Immunology, Academic Medical Centre, Amsterdam, The Netherlands.
authors.forename: S
authors.initials: S
authors.lastname: Kostense
authors.forename: F M
authors.initials: FM
authors.lastname: Raaphorst
authors.forename: D W
authors.initials: DW
authors.lastname: Notermans
authors.forename: J
authors.initials: J
authors.lastname: Joling
authors.forename: B
authors.initials: B
authors.lastname: Hooibrink
authors.forename: N G
authors.initials: NG
authors.lastname: Pakker
authors.forename: S A
authors.initials: SA
authors.lastname: Danner
authors.forename: J M
authors.initials: JM
authors.lastname: Teale
authors.forename: F
authors.initials: F
authors.lastname: Miedema
mesh_terms: D019380:Anti-HIV Agents / Q000627:therapeutic use*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D022801:Complementarity Determining Regions; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000235:genetics; D007137:Immunoglobulin alpha-Chains / Q000276:immunology*; D017493:Leukocyte Common Antigens; D018807:Polymorphism, Single-Stranded Conformational; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology*
chemical_list: D019380:Anti-HIV Agents; D022801:Complementarity Determining Regions; D007135:Immunoglobulin Variable Region; D007137:Immunoglobulin alpha-Chains; D016693:Receptors, Antigen, T-Cell, alpha-beta; D017493:Leukocyte Common Antigens