Antiretroviral therapy corrects HIV-1-induced expansion of CD8+ CD45RA+ CD2-) CD11a(bright) activated T cells.
BACKGROUND
HIV infection decreases thymic output and induces chronic T-cell activation.


OBJECTIVE
To examine the reconstitution of naive and activated T cells.


METHODS
Extended immune phenotyping of CD4(+) and CD8(+) T-cell subsets was combined with T-cell receptor rearrangement excision circle (TREC) levels and measures of T-cell receptor repertoire perturbations in CD8(+) T-cell subpopulation to define the global effect of HIV-1 on T-cell dynamics. Evaluations before and after therapy were performed in HIV-infected children and compared with those in healthy individuals.


RESULTS
Ten HIV-infected children and adolescents with a broad range of pretherapy CD4(+) T-cell counts were compared with healthy individuals. Pretherapy late activated CD8(+) T cells (CD3(+)CD8(+)CD45RA(+)CD27(-)CD11a(bright) cells) were expanded among HIV-infected subjects. Successful antiretroviral therapy increased the proportion of naive T cells (CD3(+)CD4(+)CD45RA(+)CD27(+)CD28(+) and CD3(+)CD8(+)CD45RA(+)CD27(+)CD11a(dim) cells), with a significant decrease in late activated CD8(+) T cells. The proportion of naive CD4(+) and CD8(+) T cells significantly predicted log(10) TREC copies/10(6) PBMCs in infected children and healthy control subjects, with a negative correlation in late activated CD8(+) T cells and activated CD4(+) T cells. Treatment re-established Gaussian distributions and decreased oligoclonal expansion within the Vbeta repertoire of CD8(+)CD45RA(+) T cells, but compared with that seen in healthy children, the proportion of late activated CD8(+) T cells remained increased.


CONCLUSIONS
HIV infection strikingly shifts the proportion of naive and late activated CD45RA(+)CD8(+) T cells. Homeostasis within this T-cell population reflects TREC levels and the extent of T-cell receptor Vbeta perturbations.
Department of Pathology, Immunology, and Laboratory Medicine, University of Florida College of Medicine, Gainesville, Fla, USA.
Li
L
Yin
Carina A
CA
Rodriguez
Wei
W
Hou
Olivia
O
Potter
Margaret J
MJ
Caplan
Maureen M
MM
Goodenow
John W
JW
Sleasman
D000293:Adolescent; D023241:Antiretroviral Therapy, Highly Active; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002454:Cell Differentiation; D002648:Child; D002675:Child, Preschool; D015329:Gene Rearrangement, T-Lymphocyte; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology*
D016693:Receptors, Antigen, T-Cell, alpha-beta