FoxP3+ CD8 T-cells in acute HIV infection and following early antiretroviral therapy initiation
Alexis Yero, Tao Shi, Jean‐Pierre Routy, Cécile Tremblay, Madéleine Durand, Cecilia T. Costiniuk, Mohammad‐Ali Jenabian
Abstract
Objectives Besides CD4 regulatory T-cells (Tregs), immunosuppressor FoxP3 + CD8 T-cells are emerging as an important subset of Tregs, which contribute to immune dysfunction and disease progression in HIV infection. However, FoxP3 + CD8 T-cell dynamics in acute HIV infection and following early antiretroviral therapy (ART) initiation remain understudied. Methods Subsets of FoxP3 + CD8 T-cells were characterized both prospectively and cross-sectionally in PBMCs from untreated acute (n=26) and chronic (n=10) HIV-infected individuals, early ART-treated in acute infection (n=10, median of ART initiation: 5.5 months post-infection), ART-treated in chronic infection (n=10), elite controllers (n=18), and HIV-uninfected controls (n=21). Results Acute and chronic infection were associated with increased total, effector memory, and terminally differentiated FoxP3 + CD8 T-cells, while early ART normalized only the frequencies of total FoxP3 + CD8 T-cells. We observed an increase in FoxP3 + CD8 T-cell immune activation (HLADR + /CD38 + ), senescence (CD57 + /CD28 - ), and PD-1 expression during acute and chronic infection, which were not normalized by early ART. FoxP3 + CD8 T-cells in untreated participants expressed higher levels of immunosuppressive LAP(TGF-β1) and CD39 than uninfected controls, whereas early ART did not affect their expression. The expression of gut-homing markers CCR9 and Integrin-β7 by total FoxP3 + CD8 T-cells and CD39 + and LAP(TGF-β1) + FoxP3 + CD8 T-cells increased in untreated individuals and remained higher than in uninfected controls despite early ART. Elite controllers share most of the FoxP3 + CD8 T-cell characteristics in uninfected individuals. Conclusions Although early ART normalized total FoxP3 + CD8 T-cells frequencies, it did not affect the persistent elevation of the gut-homing potential of CD39 + and LAP(TGF-β1) + FoxP3 + CD8 T-cell, which may contribute to immune dysfunction.