The Role of Dendritic Cells in Immune Control and Vaccination against γ-Herpesviruses

Christian Münz

doi:10.3390/v11121125

Abstract

The two human oncogenic γ-herpesviruses, Epstein Barr virus (EBV) and Kaposi sarcoma-associated herpesvirus (KSHV), are prototypic pathogens that are controlled by T cell responses. Despite their ubiquitous distribution, persistent infections and transforming potential, most carriers’ immune systems control them for life. Therefore, they serve as paradigms of how near-perfect cell-mediated immune control can be initiated and maintained for decades. Interestingly, EBV especially quite efficiently avoids dendritic cell (DC) activation, and little evidence exists that these most potent antigen-presenting cells of the human body are involved in the priming of immune control against this tumor virus. However, DCs can be harnessed therapeutically to expand virus-specific T cells for adoptive transfer therapy of patients with virus-associated malignancies and are also currently explored for vaccinations. Unfortunately, despite 55 and 25 years of research on EBV and KSHV, respectively, the priming of their immune control that belongs to the most robust and durable immune responses in humans still remains unclear.

Highlights

The two human oncogenic γ-herpesviruses, Epstein Barr virus (EBV) and Kaposi sarcoma-associated herpesvirus (KSHV), are prototypic pathogens that are controlled by T cell responses
KSHV cannot transform any cells in culture and does not sustain its own persistence without EBV co-infection [8,9,10]; it is associated with B cell lymphomas and the endothelial cell-derived Kaposi sarcoma in patients [11]
In contrast to cDCs, plasmacytoid dendritic cells (pDCs) are stimulated by EBV, and primary immunodeficiencies that compromise their type I IFN production or sensing of this group of cytokines are not associated with EBV pathology [14]

Summary

Introduction

The two human oncogenic γ-herpesviruses, Epstein Barr virus (EBV) and Kaposi sarcoma-associated herpesvirus (KSHV), are prototypic pathogens that are controlled by T cell responses. The lesions in the human immune system of patients with primary immunodeficiencies identify T lymphocytes as the main components of the immune control of the two γ-herpesviruses, cytotoxic CD8+ T and NK cells for EBV and IFN-γ producing T cells for KSHV [13,14,15].

Results

Conclusion