Antiretroviral therapy corrects HIV-1–induced expansion of CD8⁺CD45RA⁺CD27⁻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 log₁₀ TREC copies/10⁶ 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 Vβ 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 Vβ perturbations.

Key words: HIV-1, children, T-cell receptor, T-cell receptor rearrangement excision circles, immune reconstitution, flow cytometry, T cells

Abbreviations used: TCR, T-cell receptor, TREC, T-cell receptor rearrangement excision circle