Abstract
CD1d restricted invariant natural killer T (iNKT) cells are important in the activation and regulation of immune responses. Limited information is available regarding the functional role of iNKT cells in the human immunodeficiency virus (HIV) disease progression. α-GalCer stimulated iNKT cells were characterized for their functionality in terms of cytokine production (IFN-γ, TNF-α, IL-2, IL-4, and IL-21) and CD107a expression in HIV-1 infected [23 long-term non progressors (LTNPs), 28 progressors, 18 patients before and after suppressive anti-retroviral treatment (ART)] along with 25 HIV-1 negative subjects using multicolor flow cytometry. The functional profile of α-GalCer stimulated iNKT cells was similar in LTNPs and healthy controls. The number of LTNPs showing functional response in terms of secretion of cytokines (IFN-γ/IL2/TNF-α) and CD107a expression was significantly higher than seen in the progressors. The cytokine secretion by the stimulated iNKT cells was predominantly Th1 type. The frequencies of iNKT cells showing secretion of IFN-γ or IL2 or TNF-α or expression of CD107a were higher in LTNPs (p < 0.05 for all) and also significantly associated with lower plasma viral load (p value ranged from 0.04 to 0.003) and higher CD4 count (p value ranged from 0.02 to <0.0001). The functional profile of the iNKT cells before and after ART did not differ significantly indicating absence of restoration of iNKT cells functionality after suppressive ART. The IL-4 and IL-21 secreting iNKT cells were rare in all study populations. The presence of functional iNKT cells secreting number of cytokines in non-progressive HIV infection could be one of the multiple factors required to achieve HIV control and hence have relevance in understanding the immunity in HIV infection. The failure of restoration of the iNKT functionality after ART should be potential area of future research.
Highlights
Understanding the innate and acquired immune mechanism in human immunodeficiency virus (HIV) infection is important in designing strategies for prevention of the HIV infection and for immune therapies in infected individuals
We observed that the invariant natural killer T (iNKT) cells from 24 out of 25 (96%) HCs, 22 of 23 long-term non progressors (LTNPs) (95.65%) and 20 of 28 progressors (71.46%), and 11 of 18 anti-retroviral treatment (ART)-treated (61.11%) individuals responded to α-GalCer stimulation and secreted one or more cytokines
The functional profile in HCs (39/144 observations) and LTNPs (24/132 observations) showed higher magnitude of 3+ and 4+ grade whereas such a high magnitude was rarely observed in the progressor group (5/120 observations)
Summary
Understanding the innate and acquired immune mechanism in human immunodeficiency virus (HIV) infection is important in designing strategies for prevention of the HIV infection and for immune therapies in infected individuals. The invariant natural killer T (iNKT) cells are one of the important innate effector cells which get readily activated either upon stimulation of their TCR by CD1d presented glycolipid antigen, or by cytokines in a TCR-independent manner [1, 2] and rapidly produce an array of regulatory and pro-inflammatory cytokines [3, 4], that can subsequently activate and regulate a variety of innate and adaptive immune cells, such as dendritic cells, natural killer cells, and CD4+ and CD8+ T cells [5, 6] These cells have shown to play a role in cancer [7,8,9], autoimmune diseases [10, 11], and various infectious condition [12,13,14]. Limited information is available regarding the functional role of iNKT cells in the human immunodeficiency virus (HIV) disease progression
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