title: Distinct mechanisms of T cell reconstitution can be identified by estimating thymic volume in adult HIV-1 disease.
abstract: BACKGROUND
  We have attempted to identify factors associated with T cell reconstitution in response to highly active antiretroviral therapy.
  
  
  METHODS
  In a prospective, multicenter cohort study, we compared clinical, immune, and viral responses to an initial antiretroviral regimen in older (>or=45 years old) versus younger (18-30 years old) human immunodeficiency virus type 1-infected subjects. Multivariable linear-regression models identified independent factors associated with changes in T cell counts.
  
  
  RESULTS
  Older subjects had smaller increases in naive T cells but greater T cell receptor-excision circle DNA content after 48 weeks, despite similar virologic responses and comparable reductions in immune activation. Changes in T cell counts were associated with plasma interleukin (IL)-7 levels in subjects with low thymic scores, whereas first-phase T cell increases (perhaps mediated by redistribution to the circulation of tissue-associated lymphocytes) were associated with reductions in immune activation in subjects with high thymic scores. Reductions in immune activation were associated with reductions in spontaneous lymphocyte apoptosis.
  
  
  CONCLUSIONS
  Distinct processes may underlie T cell restoration, according to estimated thymic volumes. IL-7-mediated peripheral expansion may drive T cell restoration in persons with low thymic volume, whereas therapy-associated reversal of immune reactivation may drive T cell losses and their restoration in persons with larger thymic volume.
authors.affiliation: Division of Infectious Diseases, MetroHealth Medical Center and Case Western Reserve University, Cleveland, Ohio 44109-1998, USA. rkalayjian@metrohealth.org
authors.forename: Robert C
authors.initials: RC
authors.lastname: Kalayjian
authors.forename: John
authors.initials: J
authors.lastname: Spritzler
authors.forename: Minya
authors.initials: M
authors.lastname: Pu
authors.forename: Alan
authors.initials: A
authors.lastname: Landay
authors.forename: Richard B
authors.initials: RB
authors.lastname: Pollard
authors.forename: Vicki
authors.initials: V
authors.lastname: Stocker
authors.forename: Lena-Al
authors.initials: LA
authors.lastname: Harthi
authors.forename: Barry H
authors.initials: BH
authors.lastname: Gross
authors.forename: Isaac R
authors.initials: IR
authors.lastname: Francis
authors.forename: Susan A
authors.initials: SA
authors.lastname: Fiscus
authors.forename: Pablo
authors.initials: P
authors.lastname: Tebas
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Bosch
authors.forename: Victor
authors.initials: V
authors.lastname: Valcour
authors.forename: Michael M
authors.initials: MM
authors.lastname: Lederman
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D015331:Cohort Studies; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D015497:HIV-1; D006801:Humans; D015851:Interleukin-7 / Q000097:blood; D018655:Lymphocyte Count; D008875:Middle Aged; D009929:Organ Size; D011446:Prospective Studies; D013601:T-Lymphocytes / Q000276:immunology; D013950:Thymus Gland / Q000473:pathology*; D016896:Treatment Outcome; D014481:United States
chemical_list: D044966:Anti-Retroviral Agents; D015851:Interleukin-7