Distinct inflammation-related proteins associated with T cell immune recovery during chronic HIV-1 infection.

Chronic inflammation and T cell dysregulation persist in individuals infected with human immunodeficiency virus type 1 (HIV-1), even after successful antiretroviral treatment. The mechanism involved is not fully understood. Here, we used Olink proteomics to comprehensively analyze the aberrant inflammation-related proteins (IRPs) in chronic HIV-1-infected individuals, including in 24 treatment-naïve individuals, 33 immunological responders, and 38 immunological non-responders. T cell dysfunction was evaluated as T cell exhaustion, activation, and differentiation using flow cytometry. We identified a cluster of IRPs (cluster 7), including CXCL11, CXCL9, TNF, CXCL10, and IL18, which was closely associated with T cell dysregulation during chronic HIV-1 infection. Interestingly, IRPs in cluster 5, including ST1A1, CASP8, SIRT2, AXIN1, STAMBP, CD40, and IL7, were negatively correlated with the HIV-1 reservoir size. We also identified a combination of CDCP1, CXCL11, CST5, SLAMF1, TRANCE, and CD5, which may be useful for distinguishing immunological responders and immunological non-responders. In conclusion, the distinct inflammatory milieu is closely associated with immune restoration of T cells, and our results provide insight into immune dysregulation during chronic HIV-1 infection.

Immune Dysfunctions of CD56neg NK Cells Are Associated With HIV-1 Disease Progression.

Background: Populations of natural killer cells lacking CD56 expression [CD56neg natural killer (NK) cells] have been demonstrated to expand during human immunodeficiency virus (HIV)-1 infection. However, their phenotypic and functional characteristics have not been systematically analyzed, and their roles during disease progression remain poorly understood. Methods: In this study, 84 donors, namely 34 treatment-naïve HIV-1-infected patients (TNs), 29 HIV-1-infected patients with successful antiretroviral therapy (ARTs), and 21 healthy controls (HCs), were enrolled. The phenotypic and functional characteristics of CD56neg NK cells were analyzed using single-cell RNA-sequencing (scRNA-seq) and flow cytometry. A potential link between the characteristics of CD56neg NK cells and the clinical parameters associated with HIV-1 disease progression was examined. Results: The frequency of the CD56neg NK cell population was significantly increased in TNs, which could be partially rescued by ART. Flow cytometry analyses revealed that CD56neg NK cells were characterized by high expression of CD39, TIGIT, CD95, and Ki67 compared to CD56dim NK cells. In vitro assays revealed reduced IFN-γ and TNF-α secretion, as well as decreased expression of granzyme B and perforin in CD56neg NK cells. In line with the data obtained by flow cytometry, scRNA-seq analysis further demonstrated impaired cytotoxic activities of CD56neg NK cells. Notably, a negative correlation was observed between CD39, CD95, and Ki67 expression levels in CD56neg NK cells and CD4+ T cell counts. Conclusions: The results presented in this study indicate that the CD56neg NK cell population expanded in HIV-1-infected individuals is dysfunctional and closely correlates with HIV-1 disease progression.