Patterns of CD8 T cell clonal dominance in response to change in antiretroviral therapy in HIV-infected children.
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.
Kharbanda
M
M
Department of Pediatrics, North Shore University Hospital, New York School of Medicine, Manhasset 11030, USA.
Than
S
S
Chitnis
V
V
Sun
M
M
Chavan
S
S
Bakshi
S
S
Pahwa
S
S
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
D019380:Anti-HIV Agents; D022801:Complementarity Determining Regions; D016693:Receptors, Antigen, T-Cell, alpha-beta