Elevated Level of CD4⁺ T Cell Immune Activation in Acutely HIV-1-Infected Stage Associates With Increased IL-2...

Persistent immune activation is a striking consequence of HIV-1 infection and a driving force of CD4⁺ T cell depletion and AIDS events during chronic infection. High level of T cell immune activation associates with antiretroviral therapy (ART)-treated clinical outcomes in chronically HIV-1-infected patients. However, the role of T cell activation during acute infection stage in subsequent CD4⁺ T cell decline in the absence of ART treatment is unknown. In this study, we enrolled 26 acutely HIV-1-infected patients in the absence of ART treatment from a prospective acute HIV-1 infection cohort in Beijing (PRIMO). A comprehensive analysis of CD4⁺ and CD8⁺ T cell immune activation during acute infection stage and the clinical outcomes was studied. We found that patients with higher level of CD4⁺ T cell activation (%CD38⁺HLA-DR⁺CD4⁺ T cells) exhibited more effective function (%IL-2 production and %ki67 expression) in CD4⁺ T cells compared to those from patients without increased T cell activation at the acute phase. Direct correlations were observed between CD4⁺ T cell activation and the percentages of IL-2-producing or ki67-expressing CD4⁺ T cells in patients at the acute phase of infection. Importantly, the increased levels of CD4⁺ T cell immune activation, IL-2 production, and cycling expression during acute infection were associated with less decline of CD4⁺ T cell after 2 years of infection. However, immune exhaustion molecules in acute infection, including CD160, T cell immunoglobulin and ITIM domain, programmed cell death protein 1, and T cell immunoglobulin and mucin 3, were not associated with the CD4⁺ T cell depletion. These significant associations of CD4⁺ T cell activation were not demonstrable for CD8⁺ T cell activation at the acute phase. Taken together, our observations provide new insight into the possible role of T cell activation in preventing CD4⁺ T cell depletion during acute HIV-1 infection.