Abstract
SignificanceEvidence suggests that HIV-1 disease progression is determined in the early stages of infection. Here, preinfection invariant natural killer T (iNKT) cell levels were predictive of the peak viral load during acute HIV-1 infection (AHI). Furthermore, iNKT cells were preferentially lost in AHI. This was particularly striking in the colonic mucosa, where iNKT cells were depleted more profoundly than conventional CD4+T cells. The initiation of antiretroviral therapy during AHI-prevented iNKT cell dysregulation in peripheral blood but not in the colonic mucosa. Overall, our results support a model in which iNKT cells are early and preferential targets for HIV-1 infection during AHI.
Highlights
CD4+ T cells in peripheral blood and gut mucosal tissue
Peripheral blood mononuclear cells (PBMCs) collected preinfection, and at early infection, peak viral load (VL), VL set point, and early chronic infection corresponding to a median of 2, 16, 43, and 85 d after the first HIV-1
CCR6 have been identified as markers that are enriched in latently HIV-infected cells [42,43,44,45], we evaluated their expression on peripheral blood CD4+ invariant natural killer T (iNKT) cells of antiretroviral therapy (ART)-treated, HIV8 of 12 j PNAS
Summary
CD4+ T cells in peripheral blood and gut mucosal tissue. the impact on the predominantly CD4+ immunoregulatory invariant natural killer T (iNKT) cells during AHI remains unknown. INKT cells from peripheral blood and colonic mucosa were investigated during treated and untreated AHI. INKT cells in blood were activated and rapidly depleted in untreated AHI. Residual peripheral iNKT cells suffered a diminished responsiveness to in vitro stimulation early into chronic infection. HIV-1 DNA, as well as spliced and unspliced viral RNA, were detected in iNKT cells isolated from blood, indicating the active infection of these cells in vivo. In vitro data provided evidence of latent infection in iNKT cells. Preinfection levels of peripheral blood CD4+ iNKT cells correlated directly with the peak. These findings support a model in which iNKT cells are early targets for HIV-1 infection, driving their rapid loss from circulation and colonic mucosa
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