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.
Highlights
The SARS-Cov-2 virus developed into a worldwide pandemic in a matter of months
While T cells produce cytokines themselves, it appears that the inducers of the cytokine storm in COVID-19 seem to be infected macrophages and dendritic cells that start the cascade
Lymphopenia is common in respiratory viral infections [61] In Covid-19, while the lymphopenia is consistent in the CD4+ T cell subtype across reports, the severity of lymphopenia in the CD8+ subtype varies [62, 63]
Summary
The SARS-Cov-2 virus developed into a worldwide pandemic in a matter of months. A year after its first reporting it has infected over 121.256.160 people and killed 2.681.790 worldwide (Hopkins University 18.03.2021). The innate immune system is present since birth and defends us against a plethora of diseases and illnesses [6] While it doesn’t adapt to new challenges in an individual, it has evolved to respond to a large variety of challenges. With the phagocytosis capability comes the ability to professionally present antigens This discovery further highlights the potential importance of gd T cells in the early stages of an infection and their versatility. Their ability to phagocytose and act as antigen-presenting cells is a new discovery and needs to be further explored This could become a highly relevant topic in viral infections such as SARS-CoV 2 as well. We review the current research into gd T cells in COVID-19 as well as gd T cells as potential cell therapies in a viral infectious disease context
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