Role of costimulatory molecule CD137 in the antiviral activity of human γδ T cells against influenza virus

Abstract

Statement of the Problem: Influenza virus continues to threaten global human health with significant morbidity and mortality. Human γδ T cells, as the innate-like T lymphocytes, play an indispensable role in the host immune defense systems against virus infection. CD137 is a costimulatory molecule expressed on T cells. Although the role and function of CD137 in αβ T cells have been well studied, its role in γδ T cells has not been explored clearly. The purpose of this study is to determine the role of CD137 in the antiviral activity of human γδ T cells. Method: CD137 agonist and blocking antibody were utilized during human γδ T cells expansion and activation to study the function of CD137 signal in vitro. Rag2-/-γc-/- mice infected by influenza were used to determine the role of CD137 signal in the antiviral activity of human γδ T cells in vivo. Findings: Blocking CD137 signal could decrease the proliferation and activation of γδ T cells. Adoptive transfer of pamidronate-expanded CD137 positive γδ T cells showed more remarkable effect against influenza infection than CD137 negative in Rag2-/-γc-/- mice. Conclusion & Significance: CD137 signal can stimulate the activation and expansion of human γδ T cells, and enhance their antiviral activity against influenza virus. This study provides a novel strategy for treatment of influenza virus infection by targeting CD137 to improve the antiviral activity of human γδ T cells, and further increase the efficacy of γδ T cell-based immunotherapy by using the combination of phosphoantigen with anti-CD137 agonist.