title: T cells containing T cell receptor excision circles are inversely related to HIV replication and are selectively and rapidly released into circulation with antiretroviral treatment.
abstract: OBJECTIVE
  To examine baseline predictors of T-cell receptor rearrangement excision circle (TREC) levels and their changes during treatment with combined antiretroviral therapy.
  
  
  METHODS
  Peripheral blood and lymph node lymphocytes were examined for the presence of TREC by real-time polymerase chain reaction and circulating lymphocyte phenotypes were examined by flow cytometry. Correlates for CD4 and CD8 cell TREC levels at baseline were identified among CD4 and CD8 immunophenotypes, viral load and patient demographics; the significance of TREC changes after initiation of antiretroviral therapy was assessed.
  
  
  RESULTS
  Circulating TREC levels correlated inversely with age, with HIV RNA levels, with activation markers on circulating T cells and with naive CD4 but not CD8 cell frequencies. With initiation of antiretroviral therapy, TREC and naive T cell frequencies increased in peripheral blood during the first 2 weeks of treatment and these changes correlated negatively with TREC frequencies in lymph node aspirates, particularly among CD8 T cells.
  
  
  CONCLUSIONS
  These findings suggest that recent thymic emigrants are sequestered in lymphoid tissue during uncontrolled HIV replication and are selectively released into circulation rapidly after initiation of antiretroviral therapies.
authors.affiliation: Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio 44106, USA.
authors.forename: Mireya
authors.initials: M
authors.lastname: Diaz
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Douek
authors.forename: Hernan
authors.initials: H
authors.lastname: Valdez
authors.forename: Brenna J
authors.initials: BJ
authors.lastname: Hill
authors.forename: Dolores
authors.initials: D
authors.lastname: Peterson
authors.forename: Ian
authors.initials: I
authors.lastname: Sanne
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Piliero
authors.forename: Richard A
authors.initials: RA
authors.lastname: Koup
authors.forename: Sylvan B
authors.initials: SB
authors.lastname: Green
authors.forename: Steven
authors.initials: S
authors.lastname: Schnittman
authors.forename: Michael M
authors.initials: MM
authors.lastname: Lederman
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000494:pharmacology*; D023241:Antiretroviral Therapy, Highly Active; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects; D005260:Female; D015329:Gene Rearrangement, T-Lymphocyte; D006678:HIV / Q000302:isolation & purification / Q000502:physiology; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D006801:Humans; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000032:analysis; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology; D019562:Viral Load; D014779:Virus Replication
chemical_list: D019380:Anti-HIV Agents; D012367:RNA, Viral; D011948:Receptors, Antigen, T-Cell