TY - JOUR
T1 - Negative checkpoint regulatory molecule 2B4 (CD244) upregulation is associated with invariant natural killer T cell alterations and human immunodeficiency virus disease progression
AU - Ahmad, Fareed
AU - Shankar, Esaki M.
AU - Yong, Yean K.
AU - Tan, Hong Y.
AU - Ahrenstorf, Gerrit
AU - Jacobs, Roland
AU - Larsson, Marie
AU - Schmidt, Reinhold E.
AU - Kamarulzaman, Adeeba
AU - Ansari, Abdul W.
PY - 2017/3/27
Y1 - 2017/3/27
N2 - The CD1d-restricted invariant natural killer T (iNKT) cells are implicated in innate immune responses against human immunodeficiency virus (HIV). However, the determinants of cellular dysfunction across the iNKT cells subsets are seldom defined in HIV disease. Herein, we provide evidence for the involvement of the negative checkpoint regulator (NCR) 2B4 in iNKT cell alteration in a well-defined cohort of HIV-seropositive anti-retroviral therapy (ART) naïve, ART-treated, and elite controllers (ECs). We report on exaggerated 2B4 expression on iNKT cells of HIV-infected treatment-naïve individuals. In sharp contrast to CD4-iNKT cells, 2B4 expression was significantly higher on CD4+ iNKT cell subset. Notably, an increased level of 2B4 on iNKT cells was strongly correlated with parameters associated with HIV disease progression. Further, iNKT cells from ART-naïve individuals were defective in their ability to produce intracellular IFN-γ. Together, our results suggest that the levels of 2B4 expression and the downstream co-inhibitory signaling events may contribute to impaired iNKT cell responses.
AB - The CD1d-restricted invariant natural killer T (iNKT) cells are implicated in innate immune responses against human immunodeficiency virus (HIV). However, the determinants of cellular dysfunction across the iNKT cells subsets are seldom defined in HIV disease. Herein, we provide evidence for the involvement of the negative checkpoint regulator (NCR) 2B4 in iNKT cell alteration in a well-defined cohort of HIV-seropositive anti-retroviral therapy (ART) naïve, ART-treated, and elite controllers (ECs). We report on exaggerated 2B4 expression on iNKT cells of HIV-infected treatment-naïve individuals. In sharp contrast to CD4-iNKT cells, 2B4 expression was significantly higher on CD4+ iNKT cell subset. Notably, an increased level of 2B4 on iNKT cells was strongly correlated with parameters associated with HIV disease progression. Further, iNKT cells from ART-naïve individuals were defective in their ability to produce intracellular IFN-γ. Together, our results suggest that the levels of 2B4 expression and the downstream co-inhibitory signaling events may contribute to impaired iNKT cell responses.
KW - 2B4
KW - CD4
KW - Human immunodeficiency virus
KW - IFN-γ
KW - Inhibitory
KW - Invariant natural killer T cells
UR - http://www.scopus.com/inward/record.url?scp=85017107037&partnerID=8YFLogxK
U2 - 10.3389/fimmu.2017.00338
DO - 10.3389/fimmu.2017.00338
M3 - Article
AN - SCOPUS:85017107037
SN - 1664-3224
VL - 8
JO - Frontiers in Immunology
JF - Frontiers in Immunology
IS - MAR
M1 - 338
ER -