Figure legends
Figure 1. The heterogeneity
of the T cell immune responses after SARS-CoV-2 infection.
Upon SARS-CoV-2 infection, naïve CD4+ T cells (Th0)
differentiate into Th1 cells, CD4-GZMK, CD4-GNLY, CD4-CTLs and
TFH cells (including cytotoxic TFH and
non-cytotoxic TFH) against the virus. Then
virus-specific CD4+ T cells differentiate into memory
subsets, including TCM, TEM and
TRM cells and memory TFH cells.
CD8+ T cells, including CD8+effector T cells, CD8-KLRC1, CD8-GZMK and CD8-GNLY can directly
eliminate the virus-infected cells. Persisting stimulation of
CD8+ T-cells results in T cell exhaustion, which
express PD-1, Tim-3, CD160, LAG3, CD244 and CTLA4. After virus
clearance, virus-specific CD8+ T cells persist as
memory subsets, including TCM, TEM,
TTE and TRM cells and so on. Treg cells
are also produced and may regulate overwhelming immune responses. NKT
cells recognize glycolipid antigens presented by the HMC-I-like molecule
CD1d. Naive NKT cells, CD56+ NKT cells and
CD160+ NKT are the main subsets defensing against
virus infection. Tim-3+ NKT cells secrete high level
of IFN-g, IL-4 and IL-10 and associate with the disease severity. γδT
cells express transcriptional markers and secrete cytokines, which
perform antiviral capacity and pro-inflammatory activity. MAIT cells
recognize antigens presented by the monomorphic MHC-I related molecule,
MR1. MAIT, naïve-like and TEM-like MAIT cells express
high levels of genes involved in the inflammatory response and
IFN-stimulated genes. The genes expressed in specific cell populations
among COVID-19 patients with different clinical manifestations are shown
in gray boxes.
Figure 2. Strategies to
improve T cell responses, reverse T-cell exhaustion and reduce
inflammation for COVID-19 treatments.
(A) Strategies to improve T-cell responses. SARS-CoV-2 vaccines, such as
mRNA-based vaccine encoding SARS-CoV-2 antigen, adenovirus type
5-vectored COVID-19 (Ad5-nCoV) vaccines and whole-cell inactivated virus
vaccines can efficiently trigger virus-specific T cell responses.
SARS-CoV-2-specific T cells isolated from convalescent COVID-19
individuals are stimulated with SARS-CoV-2 peptide pool and expandin vitro for adoptive T-cell therapy. Recombinant cytokines
(including IL-7, IL-2, IFN-β1 and IFN-β2) administration help to improve
antiviral T-cell responses. (B) Strategies to reverse T-cell exhaustion.
Anti-PD-1 antibody and anti-Tim3 antibody can be used to release the
brake of CD8+T cell and NKT cell exhaustion to enhance
T cell responses. (C) Strategies to reduce inflammation. The altered
function of Th1 cells, CD4-CTLs, NKT cells, γδT cells and MAIT cells may
contribute to systemic inflammation. Anti-cytokines, IL-6 antagonists,
GM-CSF inhibitors and IL-18 blockade may reduce inflammation.