iCa2+ Flux, ROS and IL-10 Determines Cytotoxic, and Suppressor T Cell Functions in Chronic Human Viral Infections.

Abstract:

:Exhaustion of CD8+ T cells and increased IL-10 production is well-known in chronic viral infections but mechanisms leading to loss of their cytotoxic capabilities and consequent exhaustion remain unclear. Exhausted CD8+T cells also called T suppressors are highly immune suppressive with altered T cell receptor signaling characteristics that mark it exclusively from their cytotoxic counterparts. Our study found that iCa2+ flux is reduced following T cell receptor activation in T suppressor cells when compared to their effector counterpart. Importantly chronic activation of murine cytotoxic CD8+ T cells lead to reduced iCa2+ influx, decreased IFN-γ and enhanced IL-10 production and this profile is mimicked in Tc1 cells upon reduction of iCa2+ flux by extracellular calcium channel inhibitors. Further reduced iCa2+ flux induced ROS which lead to IFN-γ reduction and increased IL-10 producing T suppressors through the STAT3-STAT5 axis. The above findings were substantiated by our human data where reduced iCa2+ flux in chronic Hepatitis infections displayed CD8+ T cells with low IFN-γ and increased IL-10 production. Importantly treatment with an antioxidant led to increased IFN-γ and reduced IL-10 production in human chronic Hep-B/C samples suggesting overall a proximal regulatory role for iCa2+ influx, ROS, and IL-10 in determining the effector/ suppressive axis of CD8+ T cells.

journal_name

Front Immunol

journal_title

Frontiers in immunology

authors

Mohanty S,Barik P,Debata N,Nagarajan P,Devadas S

doi

10.3389/fimmu.2020.00083

subject

Has Abstract

pub_date

2020-03-06 00:00:00

pages

83

issn

1664-3224

journal_volume

11

pub_type

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