title: Negative Checkpoint Regulatory Molecule 2B4 (CD244) Upregulation Is Associated with Invariant Natural Killer T Cell Alterations and Human Immunodeficiency Virus Disease Progression.
abstract: 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.
authors.affiliation: Department of Clinical Immunology and Rheumatology, Hannover Medical School , Hannover , Germany.
authors.forename: Fareed
authors.initials: F
authors.lastname: Ahmad
authors.affiliation: Centre of Excellence for Research in AIDS (CERiA), University of Malaya, Kuala Lumpur, Malaysia; Department of Medical Microbiology, University of Malaya, Kuala Lumpur, Malaysia; Division of Infection Biology, Department of Life Sciences, School of Basic & Applied Sciences, Central University of Tamil Nadu (CUTN), Thiruvarur, India.
authors.forename: Esaki M
authors.initials: EM
authors.lastname: Shankar
authors.affiliation: Centre of Excellence for Research in AIDS (CERiA), University of Malaya , Kuala Lumpur , Malaysia.
authors.forename: Yean K
authors.initials: YK
authors.lastname: Yong
authors.affiliation: Centre of Excellence for Research in AIDS (CERiA), University of Malaya , Kuala Lumpur , Malaysia.
authors.forename: Hong Y
authors.initials: HY
authors.lastname: Tan
authors.affiliation: Department of Clinical Immunology and Rheumatology, Hannover Medical School , Hannover , Germany.
authors.forename: Gerrit
authors.initials: G
authors.lastname: Ahrenstorf
authors.affiliation: Department of Clinical Immunology and Rheumatology, Hannover Medical School , Hannover , Germany.
authors.forename: Roland
authors.initials: R
authors.lastname: Jacobs
authors.affiliation: Division of Molecular Virology, Department of Clinical and Experimental Medicine, Linkoping University , Linkoping , Sweden.
authors.forename: Marie
authors.initials: M
authors.lastname: Larsson
authors.affiliation: Department of Clinical Immunology and Rheumatology, Hannover Medical School , Hannover , Germany.
authors.forename: Reinhold E
authors.initials: RE
authors.lastname: Schmidt
authors.affiliation: Centre of Excellence for Research in AIDS (CERiA), University of Malaya, Kuala Lumpur, Malaysia; Department of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Adeeba
authors.initials: A
authors.lastname: Kamarulzaman
authors.affiliation: Centre of Excellence for Research in AIDS (CERiA), University of Malaya, Kuala Lumpur, Malaysia; Department of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Abdul W
authors.initials: AW
authors.lastname: Ansari
keywords: 2B4; CD4; IFN-γ; human immunodeficiency virus; inhibitory; invariant natural killer T cells