P-D10 IL-18 Reconstitutes Vg9Vd2 T Cells in HIV+ Patient Samples. (March 2017)

• Record Type: Journal Article
• Authors: Murday, Alanna; Pauza, C. David
• Is Part Of: Journal of acquired immune deficiency syndromes. Volume 74(2017)Supplement 3
• Publication Date: 2017-03
• Subjects: AIDS (Disease) -- Periodicals; Acquired Immunodeficiency Syndrome -- Periodicals; AIDS (Disease); Periodicals; 616.9792005
• DOI: 10.1097/01.qai.0000514000.04753.67
• Languages: English
• ISSNs: 1525-4135

Abstract

Abstract : The Vg9Vd2 subset of human T cells is depleted during HIV disease and not reconstituted after prolonged antiretroviral therapy (ART). Their loss is part of the immunodeficiency syndrome likely linked to increased opportunistic infections or cancer, and normal Vg9Vd2 function was observed in HIV natural virus suppressors with little to no blood viremia in the absence of ART. Our goals are to understand the mechanisms preventing full reconstitution of Vg9Vd2 T cells and discover conditions in HIV+ patients that are limiting the functionality of existing cells. We know that prolonged ART increases the T cell receptor complexity of Vg9 chains in blood, showing that de novo cell synthesis is occurring in treated HIV patients. Unfortunately, these cells remain incapable of responding to prototypical phosphoantigens even while re-gaining responsiveness to aminobisphosphonate drugs including zoledronic acid (Zol). Zol treatment increases stimulatory IPP and promotes secretion of Caspase-1 processed cytokines IL-18 and IL-1β through its effects on the NLRP3 inflammasome. The Vd2 T cell subset was particularly high for IL-18 receptor expression compared to traditional IL-18 targets CD8+ T and natural killer cells. IL-18 stimulation increased proliferation, enhanced the accumulation of effector memory cells, and increased expression of TNFa and IFNg. Vd2 T cells from HIV+ PBMCs treated with IPP proliferated much more in the presence of IL-18. Expression of CD56 and NKG2D markers also increased with IL-18 stimulation. Our results focus on the direct effects of IL-18 on Vg9Vd2 T cells. We are currently testing for links between IL-18 deficiency and the failed IPP response of Vg9Vd2 T cells from HIV+ patients treated with ART. Ultimately, we hope to translate this study to promote recovery of Vδ2 T cells in immuno-compromised HIV patients for anti-tumor and anti-viral responses.