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.