Elevated Foxp3+ double-negative T cells are associated with disease progression during HIV infection

Abstract

Persistent immune activation, which occurs during the whole course of HIV infection, plays a pivotal role in CD4+ T cells depletion and AIDS progression. Furthermore, immune activation is a key factor that leads to impaired immune reconstitution after long-term effective antiretroviral therapy (ART), and is even responsible for the increased risk of developing non-AIDS co-morbidities. Therefore, it’s imperative to identify an effective intervention targeting HIV-associated immune activation to improve disease management. Double negative T cells (DNT) were reported to provide immunosuppression during HIV infection, but the related mechanisms remained puzzled. Foxp3 endows Tregs with potent suppressive function to maintain immune homeostasis. However, whether DNT cells expressed Foxp3 and the accurate function of these cells urgently needed to be investigated. Here, we found that Foxp3+ DNT cells accumulated in untreated people living with HIV (PLWH) with CD4+ T cell count less than 200 cells/µl. Moreover, the frequency of Foxp3+ DNT cells was negatively correlated with CD4+ T cell count and CD4/CD8 ratio, and positively correlated with immune activation and systemic inflammation in PLWH. Of note, Foxp3+ DNT cells might exert suppressive regulation by increased expression of CD39, CD25, or vigorous proliferation (high levels of GITR and ki67) in ART-naive PLWH. Our study underlined the importance of Foxp3+ DNT cells in the HIV disease progression, and suggest that Foxp3+ DNT may be a potential target for clinical intervention for the control of immune activation during HIV infection.

Host immunity associated with spontaneous suppression of viremia in therapy-naïve young rhesus macaques following neonatal SHIV infection

“…IP-10 and I-TAC have been shown to be correlated with HIV-1 severity in humans as monocytes and dendritic cells (DCs) produce IP-10 in response to HIV-1 infection and promote latent infection in resting memory CD4 T cells by facilitating HIV entry and integration ( 31 – 33 ). Moreover, I-TAC is a CXCR3-ligand that when elevated in the plasma has been shown to promote CD4 T-cell (FoxP3+) activation that was also associated with severe disease progression in HIV-1 infection ( 32 , 34 ). Thus, these data implied that viral suppression following neonatal SHIV infection in RMs was associated with an immunologic milieu of less inflammatory cytokines that are linked with severe disease outcome or establishment of latent infection.…”

Consequências imunológicas e sintomatológicas decorrentes da infecção do Vírus da Imunodeficiência Humana (HIV)

“…Zhang et al (8) em seu estudo sublinhou a importância das células Foxp3+ DNT na progressão da doença pelo HIV e sugere que Foxp3+ DNT pode ser um alvo potencial para intervenção clínica para o controle da ativação imune durante a infecção pelo HIV. Para Breen et al (15) , em observações longitudinais demonstraram um impacto precoce e substancial da infecção pelo HIV no processo de envelhecimento epigenético.…”