AUTHOR=Pean Polidy , Nouhin Janin , Ratana Meng , Madec Yoann , Borand Laurence , Marcy Olivier , Laureillard Didier , Fernandez Marcelo , Barré-Sinoussi Françoise , Weiss Laurence , Scott-Algara Daniel 

TITLE=High Activation of γδ T Cells and the γδ2pos T-Cell Subset Is Associated With the Onset of Tuberculosis-Associated Immune Reconstitution Inflammatory Syndrome, ANRS 12153 CAPRI NK

JOURNAL=Frontiers in Immunology

VOLUME=10

YEAR=2019

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2019.02018

DOI=10.3389/fimmu.2019.02018

ISSN=1664-3224

ABSTRACT=<p><bold>Background:</bold> Human Immunodeficiency Virus 1 (HIV-1) and <italic>Mycobacterium Tuberculosis</italic> (Mtb) co-infected patients are commonly at risk of immune reconstitution inflammatory syndrome (IRIS) when initiating antiretroviral treatment (ART). Evidence indicates that innate immunity plays a role in TB-IRIS. Here, we evaluate the phenotype of Gamma-delta (γδ) T cells and invariant Natural Killer (iNK) T cells in tuberculosis-associated IRIS.</p><p><bold>Methods:</bold> Forty-eight HIV+/TB+ patients (21 IRIS) and three control groups: HIV–/TB– (HD, <italic>n</italic> = 11), HIV+/TB– (<italic>n</italic> = 26), and HIV–/TB+ (<italic>n</italic> = 22) were studied. Samples were taken at ART initiation (week 2 of anti-tuberculosis treatment) and at the diagnosis of IRIS for HIV+/TB+; before ART for HIV+/TB-, and at week 2 of anti-tuberculosis treatment for HIV–/TB+ patients. γδ T cells and Invariant natural killer T (iNKT) cells were analyzed by flow cytometry.</p><p><bold>Results:</bold> Before ART, IRIS, and non-IRIS patients showed a similar proportion of γδ<sup>pos</sup> T and iNKT cells. HLA-DR on γδ<sup>pos</sup> T cells and δ2<sup>pos</sup>γδ<sup>pos</sup> T cells was significantly higher in TB-IRIS vs. non-IRIS patients and controls (<italic>p</italic> &lt; 0.0001). NKG2D expression on γδ<sup>pos</sup> T cells and the δ2<sup>pos</sup>γδ<sup>pos</sup> T cell subset was lower in HIV+/TB+ patients than controls. CD158a expression on γδ<sup>pos</sup> T cells was higher in TB-IRIS than non-IRIS (<italic>p</italic> = 0.02), HIV+/TB–, and HIV–/TB- patients.</p><p><bold>Conclusion:</bold> The higher activation of γδ<sup>pos</sup>T cells and the γδ2<sup>pos</sup>γδ<sup>pos</sup> T cell subset suggests that γδ T cells may play a role in the pathogenesis of TB-IRIS.</p>