γδT Cells Are Required for CD8+ T Cell Response to Vaccinia Viral Infection.

Rui Dai,Xiaopei Huang,Yiping Yang

doi:10.3389/fimmu.2021.727046

Rui Dai, Xiaopei Huang + Show 1 more

Open Access

https://doi.org/10.3389/fimmu.2021.727046

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Abstract

Vaccinia virus (VV) is the most studied member of the poxvirus family, is responsible for the successful elimination of smallpox worldwide, and has been developed as a vaccine vehicle for infectious diseases and cancer immunotherapy. We have previously shown that the unique potency of VV in the activation of CD8+ T cell response is dependent on efficient activation of the innate immune system through Toll-like receptor (TLR)-dependent and -independent pathways. However, it remains incompletely defined what regulate CD8+ T cell response to VV infection. In this study, we showed that γδT cells play an important role in promoting CD8+ T cell response to VV infection. We found that γδT cells can directly present viral antigens in the context of MHC-I for CD8+ T cell activation to VV in vivo, and we further demonstrated that cell-intrinsic MyD88 signaling in γδT cells is required for activation of γδT cells and CD8+ T cells. These results illustrate a critical role for γδT cells in the regulation of adaptive T cell response to viral infection and may shed light on the design of more effective vaccine strategies based on manipulation of γδT cells.

Highlights

Vaccinia virus (VV), an enveloped double-stranded DNA virus, is a member of the Orthopoxvirus genus of the Poxviridae family
We found that in both spleen (Figure 1A) and peritoneal cavity (Figure 1B), IFN-g+ gdT cell count reached its peak around day 4 following VV infection, with subsequent decline in the days following
We found that naïve gdT cells secreted IFN-g after stimulation, we subsequently determined IFN-g gating within each experiment against fluorescence minus one (FMO) controls (Figures 1C, D), and between inoculated versus naïve mice

Summary

Introduction

Vaccinia virus (VV), an enveloped double-stranded DNA virus, is a member of the Orthopoxvirus genus of the Poxviridae family It has approximately a 200kb genome that encodes all the proteins required for cytoplasmic viral replication in host cells [1]. TLR-independent production of type I interferons (IFNs) is important for efficient CD8+ T cell responses [7, 10]. Despite these advances, the mechanisms by conventional antigen-presenting cells are unable to fully explain the unique potency of VV in the activation of CD8+ T cell responses

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