May 2018 | Volume 9 | Article 1152 1 ORIGINAL RESEARCH published: 24 May 2018 doi: 10.3389/fmmu.2018.01152 Frontiers in Immunology | www.frontiersin.org Edited by: Luc Van Kaer, Vanderbilt University, United States Reviewed by: Dominic Paquin Proulx, United States Military HIV Research Program, United States Jagannadha K. Sastry, University of Texas MD Anderson Cancer Center, United States *Correspondence: Madhuri Thakar mthakar.nari@gov.in, mthakar@nariindia.org Specialty section: This article was submitted to T Cell Biology, a section of the journal Frontiers in Immunology Received: 10 March 2018 Accepted: 08 May 2018 Published: 24 May 2018 Citation: Singh D, Ghate M, Godbole S, Kulkarni S and Thakar M (2018) Functional Invariant Natural Killer T Cells Secreting Cytokines Are Associated With Non-Progressive Human Immunodefciency Virus-1 Infection but Not With Suppressive Anti-Retroviral Treatment. Front. Immunol. 9:1152. doi: 10.3389/fmmu.2018.01152 Functional Invariant Natural Killer T Cells Secreting Cytokines Are Associated With Non-Progressive Human Immunodefciency Virus-1 Infection but Not With Suppressive Anti-Retroviral Treatment Dharmendra Singh 1 , Manisha Ghate 2 , Sheela Godbole 3 , Smita Kulkarni 4 and Madhuri Thakar 1 * 1 Department of Immunology, National AIDS Research Institute, Pune, India, 2 Department of Clinical Sciences, National AIDS Research Institute, Pune, India, 3 Department of Epidemiology and Biostatistics, National AIDS Research Institute, Pune, India, 4 Department of Virology, National AIDS Research Institute, Pune, India Background: CD1d restricted invariant natural killer T (iNKT) cells are important in the activation and regulation of immune responses. Limited information is available regard- ing the functional role of iNKT cells in the human immunodefciency virus (HIV) disease progression. Methodology: α-GalCer stimulated iNKT cells were characterized for their function- ality 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 fow cytometry. Results: The functional profle 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 signifcantly 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 signifcantly 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 profle of the iNKT cells before and after ART did not differ signifcantly 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. Conclusion: 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 con- trol 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. Keywords: invariant natural killer T cells, cytokines, CD1d, long-term non progressors, human immunodefciency virus