Role of human γδ-T cells in the generation of influenza virus-specific antibodies in vitro

Abstract

Influenza virus continues to threaten global human health with significant morbidity and mortality. Induction of influenza virus-specific neutralizing antibodies by vaccines has been the most efficient strategy in saving lives and limiting viral spread. However, the efficacy of vaccines is still limited by the highly frequent mutations in the viruses and the immune status of the host and some side effects of vaccination. Therefore, developing alternative strategies to enhance the induction of influenza virus-specific neutralizing antibodies is beneficial to prevent influenza virus infection.

Human Vγ9Vδ2 T cells as a critical component of the innate immune system exhibit profound cytotoxic activity to infected cells, infectious pathogens or tumor cells. In addition, they are also accepted as crucial player in the adaptive immune system, which display potent capacities to help B cells to produce antibodies. However, little is known about the role of human Vγ9Vδ2 T cells in helping the production of influenza virus-specific antibodies.

In this study, we firstly found that resting human Vγ9Vδ2 T cells play a comparable role in total IgM and IgG antibody productions as conventional 〖CD4〗^+ T cells, while have little effects on influenza virus-specific IgM and IgG antibody productions, which might be due to their small quantity and rest status in normal PBMCs. However, human Vγ9Vδ2 T cells can be specifically activated and expanded by phosphoantigens, such as pamidronate, a registered drug used in clinic for treating osteoporosis. Therefore, we co-cultured human B cells and UV-inactivate H9N2 influenza virus-pulsed autologous monocyte-derived dendritic cells (MDDCs) with autologous pamidronate-expanded Vγ9Vδ2 T cells (PAMVγ9Vδ2 T cells). We found that after co-culture, B cells with the help of PAMVγ9Vδ2 T cells produced higher levels of total IgM, IgG and H9N2 influenza virus-specific IgM, IgG antibody than B cells without any T cells help, although the levels of total IgM, IgG and H9N2 influenza virus-specific IgG antibody were lower than that with the help of CD4+ T cells. Moreover, the PAM-Vγ9Vδ2 T cells were activated and expressed some follicular helper T cell (Tfh cell) associated molecules (ICOS, CD40L) after co-culture.

In summary, we found that phosphoantigen pamidronate expanded-Vγ9Vδ2 T cells can help B cells to produce both total and influenza virus-specific antibody, which provide evidences for the helper role of human Vγ9Vδ2 T cells in humoral immune responses.