Virus Res. 2024 Jan 09. pii: S0168-1702(24)00008-X. [Epub ahead of print] 199315
Xiaobo Huang,
Jonas Kantonen,
Kirsten Nowlan,
Ngoc Anh Nguyen,
Suvi T Jokiranta,
Suvi Kuivanen,
Nelli Heikkilä,
Shamita Mahzabin,
Anu Kantele,
Olli Vapalahti,
Liisa Myllykangas,
Santtu Heinonen,
Mikko I Mäyränpää,
Tomas Strandin,
Eliisa Kekäläinen.
Prolonged T cell lymphopenia is common in COVID-19, caused by SARS-CoV-2. While the mechanisms of lymphopenia during COVID-19 remain elusive, it is especially pronounced in a specialized innate-like T cell population called Mucosal Associated Invariant T cells (MAITs). MAITs has been suggested to express Angiotensin-Converting Enzyme 2 (ACE2), which is the well-known cellular receptor for SARS-CoV-2. However, it is still unclear if SARS-CoV-2 can infect or affect MAIT cells directly. In this study, we performed multicolor flow cytometry on peripheral blood mononuclear cells obtained from COVID-19 patients to assess the frequencies of CD8+Vα7.2+CD161+ MAIT subsets at acute and convalescent disease phases. The susceptibility of MAITs and T cells to direct exposure by SARS-CoV-2 was analysed using cells isolated from healthy donor buffy coats by viability assays, virus-specific RT-PCR, and flow cytometry. In situ lung immunofluorescence was used to evaluate retention of T cells, especially MAIT cells, in lung tissues during acute COVID-19. Our study confirms previous reports indicating that circulating MAITs are activated, and their frequency is declined in patients with acute SARS-CoV-2 infection, whereas an accumulation of MAITs and T cells was seen in the lung tissue of individuals with fatal COVID-19. However, despite a fraction of MAITs found to express ACE2, no evidence for the susceptibility of MAITs for direct infection or activation by SARS-CoV-2 particles was observed. Thus, their activation and decline in the circulation is most likely explained by indirect mechanisms involving other immune cells and cytokine-induced pro-inflammatory environment but not by direct exposure to viral particles at the infection site.
Keywords: COVID-19; Mucosal Associated Invariant T cells; SARS-CoV-2; lymphopenia; viral challenge