CD1-Restricted T Cells During Persistent Virus Infections: "Sympathy for the Devil".

Günther Schönrich,Martin J Raftery

doi:10.3389/fimmu.2018.00545

Abstract

Some of the clinically most important viruses persist in the human host after acute infection. In this situation, the host immune system and the viral pathogen attempt to establish an equilibrium. At best, overt disease is avoided. This attempt may fail, however, resulting in eventual loss of viral control or inadequate immune regulation. Consequently, direct virus-induced tissue damage or immunopathology may occur. The cluster of differentiation 1 (CD1) family of non-classical major histocompatibility complex class I molecules are known to present hydrophobic, primarily lipid antigens. There is ample evidence that both CD1-dependent and CD1-independent mechanisms activate CD1-restricted T cells during persistent virus infections. Sophisticated viral mechanisms subvert these immune responses and help the pathogens to avoid clearance from the host organism. CD1-restricted T cells are not only crucial for the antiviral host defense but may also contribute to tissue damage. This review highlights the two edged role of CD1-restricted T cells in persistent virus infections and summarizes the viral immune evasion mechanisms that target these fascinating immune cells.

Highlights

The majority of virus infections are self-limiting
The importance of crosstalk between invariant NKT (iNKT) cells and monocytederived dendritic cells (DCs) is underlined by the observation that both cell types are programmed to migrate to inflamed peripheral tissue [55, 108,109,110]
negative factor (Nef)-mediated CD1a downregulation might require the interaction of Nef with hematopoietic cell kinase and p21-activated kinase 2, which are both expressed in immature DCs [241]

Summary

INTRODUCTION

The majority of virus infections are self-limiting. Immunocompetent hosts often eliminate the invading pathogen without causing permanent tissue damage. In vitro-studies revealed that after recognition of self or foreign lipid antigens group 1 CD1-restricted T cells become cytoloytic and secrete large amounts of cytokines such as IFN-γ and TNF-α [44,45,46] These cytokines have a profound antiviral effect and play a pivotal role in controlling persistent virus infections [47]. The importance of crosstalk between iNKT cells and monocytederived DCs is underlined by the observation that both cell types are programmed to migrate to inflamed peripheral tissue [55, 108,109,110] Many persistent viruses such as herpes simplex virus type 1 (HSV-1), HSV-2 and HCMV target monocytederived DCs to induce apoptosis or impair antigen presentation through MHC class I molecules [111,112,113]. The protective and pathogenic role of CD1d-restricted T cells has been investigated in several animal models of persistent virus infections (see Table 1)

Key findings

Findings

CONCLUSION AND FUTURE DIRECTIONS