Antiretroviral therapy initiation during primary HIV infection enhances both CD127 expression and the proliferative capacity of HIV-specific CD8+ T cells

Abstract

Objectives: HIV-specific CD8+ T cells from patients with primary HIV infection (PHI) and after antiretroviral therapy initiation were evaluated for CD127 expression and proliferative capacity and were compared with cells from chronically-infected patients, including long-term nonprogressors and HIV controllers.

Methods: We studied 30 patients with PHI (from the Agence Nationale de Recherche sur le SIDA Primo-infection Cohort) and 33 patients with chronic HIV infection (including nonprogressor patients from the Agence Nationale de Recherche sur le SIDA ALT Cohort and the Agence Nationale de Recherche sur le SIDA HIV Controllers Study Group). HIV-specific CD8+ T cells were identified by costaining with HIV human leukocyte antigen class I pentamers. CD127 expression was assessed by flow cytometry and cell proliferation by carboxyfluorescein succinimidyl ester labeling.

Results: During PHI, most HIV-specific CD8+ T cells coexpressed CD27 and CD45RO, were highly activated, and showed weak Bcl-2 expression. Their CD127 expression was very low and correlated negatively both with HIV RNA and DNA levels and with expression of the activation marker CD38. CD127 expression correlated positively with CD4 cell count, Bcl-2 expression and proliferative capacity. Strong CD127 expression was observed in the two groups of chronically-infected nonprogressors. CD127 expression on HIV-specific CD8+ T cells increased in early-treated PHI patients, reaching levels similar to those observed in nonprogressors. In parallel, these cells acquired strong proliferative capacity. No change in CD127 expression or proliferative potential was observed in untreated patients.

Conclusion: Early antiretroviral therapy initiation enhances CD127 expression on HIV-specific CD8+ T cells, reaching levels similar to those observed in aviremic nonprogressors, and restores their proliferative capacity.