title: Persistent alterations in the T-cell repertoires of HIV-1-infected and at-risk uninfected men.
abstract: OBJECTIVE
  We examined the association between immunogenic exposure and T-cell receptor (TCR) diversity to more clearly assess the impact of HIV-1 infection on the T-cell repertoire.
  
  
  METHODS
  : To estimate the extent of T-cell clonality attributable to HIV-1 infection, we evaluated T-cell repertoires in low-risk and at-risk seronegative men and HIV-1 seropositive men by assessment of T-cell receptor beta-chain (TCR beta) complimentary determining region 3 (CDR3) lengths.
  
  
  RESULTS
  The frequency of T-cell clonality in both HIV-1 infected and at-risk uninfected men was elevated in comparison to low-risk uninfected men. Among low-risk and at-risk seronegative, and HIV-1 seropositive men, clonal expansions were present in 3, 8, and 10% of CD4+ CDR3 lengths, and 18, 22, and 28% of CD8+ CDR3 lengths respectively. In addition, the longitudinal conservation of clonal expansions was observed in at-risk seronegative men. Based on comparisons to at-risk seronegative men, we estimate that at-risk seropositive men with chronic HIV-1 infection exhibit a 27% increase in the number of expanded CD8+ CDR3 lengths.
  
  
  CONCLUSIONS
  These findings provide an approximation of the magnitude of the T-cell response in individuals undergoing chronic HIV-1 infection and demonstrate a significant association between the history of immunogenic challenge and the magnitude of clonality within the T-cell repertoire. In addition, these findings underscore the necessity of selecting controls with similar antigenic exposure histories when investigating T-cell dynamics in HIV-infected individuals.
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California 90095, USA.
authors.forename: M Scott
authors.initials: MS
authors.lastname: Killian
authors.forename: Joanita
authors.initials: J
authors.lastname: Monteiro
authors.forename: Jose
authors.initials: J
authors.lastname: Matud
authors.forename: Lance E
authors.initials: LE
authors.lastname: Hultin
authors.forename: Mary Ann
authors.initials: MA
authors.lastname: Hausner
authors.forename: Otto O
authors.initials: OO
authors.lastname: Yang
authors.forename: Peter K
authors.initials: PK
authors.lastname: Gregersen
authors.forename: Roger
authors.initials: R
authors.lastname: Detels
authors.forename: Janis V
authors.initials: JV
authors.lastname: Giorgi
authors.forename: Beth D
authors.initials: BD
authors.lastname: Jamieson
mesh_terms: D000704:Analysis of Variance; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002908:Chronic Disease; D005434:Flow Cytometry; D015658:HIV Infections / Q000276:immunology*; D018023:HIV Seronegativity / Q000276:immunology; D006679:HIV Seropositivity / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D018451:Homosexuality, Male; D006801:Humans; D016130:Immunophenotyping; D008297:Male; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D012307:Risk Factors; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D016693:Receptors, Antigen, T-Cell, alpha-beta