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AIDS. 2000 Oct 20;14(15):2229-38.

Patterns of CD8 T cell clonal dominance in response to change in antiretroviral therapy in HIV-infected children.

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1
Department of Pediatrics, North Shore University Hospital, New York School of Medicine, Manhasset 11030, USA.

Abstract

OBJECTIVE:

To examine the influence of change in antiretroviral therapy (ART) on patterns of CD8 T cell clonal dominance in HIV-infected children.

DESIGN:

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.

CONCLUSION:

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.

[Indexed for MEDLINE]

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