Antiretroviral therapy corrects HIV-1-induced expansion of CD8+ CD45RA+ CD2-) CD11a(bright) activated T cells.

Published

Journal Article

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. CONCLUSION: 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.

Full Text

Duke Authors

Cited Authors

  • Yin, L; Rodriguez, CA; Hou, W; Potter, O; Caplan, MJ; Goodenow, MM; Sleasman, JW

Published Date

  • July 2008

Published In

Volume / Issue

  • 122 / 1

Start / End Page

  • 166 - 172.e2

PubMed ID

  • 18538835

Pubmed Central ID

  • 18538835

Electronic International Standard Serial Number (EISSN)

  • 1097-6825

Digital Object Identifier (DOI)

  • 10.1016/j.jaci.2008.04.029

Language

  • eng

Conference Location

  • United States