MAIT cells
MAIT cells, a subset of innate-like T cells, are primarily located in
mucosal epithelia defending against microbial activity and infection by
recognizing antigens presented by the monomorphic MHC-I related
molecule, MR1 [20, 81]. Firstly, the transcriptional profiles of
MAIT cells from patients with severe disease were different compared
with those from patients with moderate disease, with downregulated
canonical markers SLC4A10 and TRAV1-2 and upregulated
genes TRBV9, TRAV8-2, S100A8, GZMH, S100A9, KLF6, CD8B, KLRD1,
IGLV3-19 and JCHAIN (Figure 1). The differentially
expressed genes might correlate with the disease severity [20].
Secondly, the frequency of MAIT-cells in peripheral blood was reduced in
a COVID-19 severity-dependent manner [70, 75, 82]. The proportion of
naive
(CD45RA+CD197+)-like
MAIT cells was significantly decreased and the proportion of
TEM (CD45RA-CD197-)-like MAIT cells was significantly increased in
patients with severe COVID-19 compared to healthy controls (Figure 1)
[83]. The cause of the loss of MAIT cells in peripheral blood of
severe COVID-19 patients remained unknown. ScRNA-seq analysis revealed
that high levels of molecules related to apoptosis and pyroptosis might
contribute to the decline of peripheral MAIT cells. In addition, high
level of cell chemotaxis expressed on peripheral MAIT cells was observed
in patients with severe disease, suggesting the increased migration of
MAIT cells to inflammatory tissues. Hence, the pulmonary recruitment may
contribute to MAIT cell reduction [20, 83]. Thirdly, despite reduced
abundances, MAIT cells showed increased activation in severe and
non-severe COVID-19 patients [23]. Notably, the activation levels of
MAIT cells in severe cases were less than those in moderate and
convalescent cases [20]. The high activation of MAIT cells suggested
consistent responses to SARS-CoV-2 infection.
MAIT cells from patients in intensive care unit (ICU) expressed higher
levels of genes involved in the inflammatory response (NFKBIA,
TXNIP and CD69 ) and decreased levels of IFITM1 [84].
Moreover, the cytotoxic responses genes (GNLY, PRDM1 andPRF1 ) and the key transcription factors (HOBIT andTBX21 ) that induce and maintain cellular production of GZMB were
upregulated in ICU patients [84]. Besides, other study found that
IFN-stimulated genes, such as IFITM1, IFITM2, and IFITM3,exhibited greater levels in peripheral MAIT cells of COVID-19 patients
compared to those from healthy controls. Blocking IFN-α rescued MAIT
cell function in patients with severe COVID-19 [84]. MAIT cells in
pregnant COVID-19 patients showed higher proinflammatory profile
(IFNGR1, STAT1 , TNFRSF1B, TNFAIP3, and TNFSF8 ), and higher
chemotaxis signature (CXCR4 ) than the non-pregnant COVID-19
patients [75]. Altered MAIT cell functions may contribute to disease
severity through influencing IFN-α–IL-18 imbalance [84]. Herein,
MAIT cells serve as a double‐edged sword mediating both protective and
pathogenic processes after SARS-CoV-2 infection, and MAIT cell-based
therapies worth considering.
T cell based therapeutic options for
COVID-19
Several
therapeutic approaches, such as antivirals [85-88] and monoclonal
antibodies targeting SARS-CoV-2 [85] have been used for COVID-19
treatment. Strategies focused on improving T cell responses and Th1
responses, reversing T-cell exhaustion and settling inflammation are
promising approaches for COVID-19 treatments (Figure 2).