Quis Custodiet Ipsos Custodes? Regulation of Cell-Mediated Immune Responses Following Viral Lung Infections

Abstract

Viral lung infections are leading causes of morbidity and mortality. Effective immune responses to these infections require precise immune regulation to preserve lung function after viral clearance. One component of airway pathophysiology and lung injury associated with acute respiratory virus infection is effector T cells, yet these are the primary cells required for viral clearance. Accordingly, multiple immune mechanisms exist to regulate effector T cells, limiting immunopathology while permitting clearance of infection. Much has been learned in recent years about regulation of T cell function during chronic infection and cancer, and it is now clear that many of these mechanisms also control inflammation in acute lung infection. In this review, we focus on regulatory T cells, inhibitory receptors, and other cells and molecules that regulate cell-mediated immunity in the context of acute respiratory virus infection.

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“…Journal Pre-proof J o u r n a l P r e -p r o o f 13 by killing the infected epithelial cells, and cytotoxic CD8+ T cells produce and release pro-inflammatory cytokines which induce cell apoptosis [46]. Both the pathogen (CoV) and cell apoptosis trigger and amplify the immune response.…”

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“…From the moment the virus is inhaled and infects the epithelial cells of the respiratory tract, dendritic cells phagocytose the virus and present antigens to T cells. The resultant effector T cells function by killing the infected epithelial cells, and cytotoxic CD8+ T cells produce and release pro-inflammatory cytokines, which induce cell apoptosis [48]. Both the pathogen (CoV) and cell apoptosis trigger and amplify the immune response.…”

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“…NKT cells embody a mixed population of T cells that possess killing properties of both NK and T cells and form a bridge between the innate and adaptive immune system. During viral infections, NKT cells exert effector functions but also regulate immune responses in order to limit lung inflammation [41]. Interestingly, a recent study by Gaya et al showed that NKT cells promote B cell immunity during viral infections via the release of IL-4 [143].…”

“…Virus-specific CD8+ T cells can selectively eliminate infected cells. Following peak expansion, the CD8+ T cells numbers shrink and a memory population of virus-specific CD8+ T cells remains in the lungs [41]. hMPV infection results in the accumulation of hMPV-specific cytotoxic and IFN-γ positive effector cells in both the airways and lungs seven days post infection.…”

“…Upon DC migration to the regional draining lymph node, the processed viral antigen can be presented to CD4+ and CD8+ T cells. The activated effector T cells with a matching T cell receptor subsequently expand and travel to the lung parenchyma where they can eliminate the infected epithelial cells [41].…”