title: Patterns of CD8 T cell clonal dominance in response to change in antiretroviral therapy in HIV-infected children.
abstract: OBJECTIVE
  To examine the influence of change in antiretroviral therapy (ART) on patterns of CD8 T cell clonal dominance in HIV-infected children.
  
  
  METHODS
  Seventeen HIV-infected children with plasma virus loads between 3.1 and 5.7 log10 were investigated before and after changes in ART.
  
  
  METHODS
  CDR3 spectratyping was performed in 22 T cell receptor (TCR) Vbeta subfamilies by multiplex polymerase chain reaction (PCR) in purified peripheral blood CD8 T cells in conjunction with CD4 cell counts, plasma HIV-RNA copies and lymphoproliferative assays (LPA).
  
  
  RESULTS
  CD8 T cell clonal dominance in two or more Vbeta families was present in eight out of 17 children. After a change in therapy, 13 patients (76%) acquired new clones whereas three patients (17.6%) showed a loss in CD8 cell clones. An increase in the numbers of dominant clones correlated with an increase in percentage CD4 cell counts (P < 0.001) and with improved LPA responses to tetanus (P < 0.05) and alloantigens (P < 0.01). CD4 cell increase was associated with an initial mean gain of 3.1+/-2.1 CD8 cell clones, independent of a virological response. A loss of CD8 cell clones or failure to achieve CD4 T cell increase was associated with failure to achieve virological suppression.
  
  
  CONCLUSIONS
  Children with chronic HIV infection manifest CD8 T cell clonal dominance, which appears to be dependent upon the adequacy of the CD4 cells. With optimization of therapy, a gain in clonal dominance is the predominant response, except in situations of failure to contain viral replication.
authors.affiliation: Department of Pediatrics, North Shore University Hospital, New York School of Medicine, Manhasset 11030, USA.
authors.forename: M
authors.initials: M
authors.lastname: Kharbanda
authors.forename: S
authors.initials: S
authors.lastname: Than
authors.forename: V
authors.initials: V
authors.lastname: Chitnis
authors.forename: M
authors.initials: M
authors.lastname: Sun
authors.forename: S
authors.initials: S
authors.lastname: Chavan
authors.forename: S
authors.initials: S
authors.lastname: Bakshi
authors.forename: S
authors.initials: S
authors.lastname: Pahwa
mesh_terms: D000293:Adolescent; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D022801:Complementarity Determining Regions / Q000235:genetics; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D007223:Infant; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D022801:Complementarity Determining Regions; D016693:Receptors, Antigen, T-Cell, alpha-beta