IFN\u03b3-producing CD4+ T lymphocytes: the double-edged swords in tuberculosis

Pawan Kumar

doi:10.1186/s40169-017-0151-8

Abstract

IFNγ-producing CD4+ T cells (IFNγ+CD4+ T cells) are the key orchestrators of protective immunity against Mycobacterium tuberculosis (Mtb). Primarily, these cells act by enabling Mtb-infected macrophages to enforce phagosome-lysosome fusion, produce reactive nitrogen intermediates (RNIs), and activate autophagy pathways. However, TB is a heterogeneous disease and a host of clinical and experimental findings has also implicated IFNγ+CD4+ T cells in TB pathogenesis. High frequency of IFNγ+CD4+ T cells is the most invariable feature of the active disease. Active TB patients mount a heightened IFNγ+CD4+ T cell response to mycobacterial antigens and demonstrate an IFNγ-inducible transcriptomic signature. IFNγ+CD4+ T cells have also been shown to mediate TB-associated immune reconstitution inflammatory syndrome (TB–IRIS) observed in a subset of antiretroviral therapy (ART)-treated HIV- and Mtb-coinfected people. The pathological face of IFNγ+CD4+ T cells during mycobacterial infection is further uncovered by studies in the animal model of TB–IRIS and in Mtb-infected PD-1−/− mice. This manuscript encompasses the evidence supporting the dual role of IFNγ+CD4+ T cells during Mtb infection and sheds light on immune mechanisms involved in protection versus pathogenesis.

Highlights

Tuberculosis (TB) continues to be one of the major causes of morbidity and mortality worldwide [1]
A key role in CD4+ T cell-mediated macrophage activation can be attributed to IFNγ, which helps in Mycobacterium tuberculosis (Mtb) clearance by inducing inducible nitric oxide synthase (iNOS) expression and enforcing phagosomelysosome fusion [2]. TH1-polarized CD4+ T cells are the main source of IFNγ during mycobacterial infections
With increasing recognition of TB as a heterogeneous disease [2], IFNγ+CD4+ T cells have been implicated in TB pathogenesis

Summary

Introduction

Tuberculosis (TB) continues to be one of the major causes of morbidity and mortality worldwide [1]. Both human and animal studies have established that IFNγ+CD4+ T cells are the key mediators of protective immunity against Mtb. It has been shown that mice deficient in IFNγ are unable to control low-dose Mtb infection and succumb to the progressive disease [7,8,9]. Studies with Mtb-infected macrophages have shown that IFNγ signalling can activate these cells to enforce phagosome maturation and eliminate the intracellular bacilli [25].

Results

Conclusion