Gamma Delta T Cells and Their Involvement in COVID-19 Virus Infections

Abstract

The global outbreak of the SARS-Cov-2 virus in 2020 has killed millions of people worldwide and forced large parts of the world into lockdowns. While multiple vaccine programs are starting to immunize the global population, there is no direct cure for COVID-19, the disease caused by the SARS-Cov-2 infection. A common symptom in patients is a decrease in T cells, called lymphopenia. It is as of yet unclear what the exact role of T cells are in the immune response to COVID-19. The research so far has mainly focused on the involvement of classical αβ T cells. However, another subset of T cells called γδ T cells could have an important role to play. As part of the innate immune system, γδ T cells respond to inflammation and stressed or infected cells. The γδ T cell subset appears to be particularly affected by lymphopenia in COVID-19 patients and commonly express activation and exhaustion markers. Particularly in children, this subset of T cells seems to be most affected. This is interesting and relevant because γδ T cells are more prominent and active in early life. Their specific involvement in this group of patients could indicate a significant role for γδ T cells in this disease. Furthermore, they seem to be involved in other viral infections and were able to kill SARS infected cells in vitro. γδ T cells can take up, process and present antigens from microbes and human cells. As e.g. tumour-associated antigens are presented by MHC on γδ T cells to classical T-cells, we argue here that it stands to reason that also viral antigens, such as SARS-Cov-2-derived peptides, can be presented in the same way. γδ T cells are already used for medical purposes in oncology and have potential in cancer therapy. As γδ T cells are not necessarily able to distinguish between a transformed and a virally infected cell it could therefore be of great interest to investigate further the relationship between COVID-19 and γδ T cells.

Keywords: COVID-19; SARS-Cov-2; T cells; gamma-delta T cell; lymphopenia.

Figure 1

Schematic of the function of γδ T cells. γδ T cells can be activated by stress signals from infected or tumour cells. Stressed or infected cells can express MICA and MICB which γδ T cells can recognise via the NKG2D receptor. Furthermore, the overexpression of certain molecules such as IPP can be recognised through the γδ TCR by recognising BTN3A and BTN2A on stressed or infected cells. γδ T cells can respond via different channels. This can be the production of cytokines (IFN-γ, TNF-α, IL-6, IL-17) or cytolysis (Perforin, Granzyme). Additionally, γδ T cells can interact with other immune cells and present antigens. Created by BioRender.

Figure 2

Schematic of what effects γδ T cells during a Covid-19 infection. γδ T cells levels are low in Covid-19 patients which is characterized by Lymphopenia. They seem to be exhausted which is detected via the exhaustion marker PD-1. They also seem to be heavily activated which is shown through activation markers CD25, CD69 and IL-18. However, γδ T cells produce high amounts of IFN- γ in response to Covid-19. Created by BioRender.