Affiliations 

  • 1 Department of Clinical Immunology and Rheumatology, Hannover Medical School , Hannover , Germany
  • 2 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
  • 3 Centre of Excellence for Research in AIDS (CERiA), University of Malaya , Kuala Lumpur , Malaysia
  • 4 Division of Molecular Virology, Department of Clinical and Experimental Medicine, Linkoping University , Linkoping , Sweden
  • 5 Centre of Excellence for Research in AIDS (CERiA), University of Malaya, Kuala Lumpur, Malaysia; Department of Medicine, University of Malaya, Kuala Lumpur, Malaysia
Front Immunol, 2017;8:338.
PMID: 28396665 DOI: 10.3389/fimmu.2017.00338

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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.