Browse > Article
http://dx.doi.org/10.14348/molcells.2021.0079

Phenotypes and Functions of SARS-CoV-2-Reactive T Cells  

Jung, Min Kyung (Laboratory of Immunology and Infectious Diseases, Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST))
Shin, Eui-Cheol (Laboratory of Immunology and Infectious Diseases, Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST))
Publication Information
Molecules and Cells / v.44, no.6, 2021 , pp. 401-407 More about this Journal
Abstract
Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), which is an ongoing pandemic disease. SARS-CoV-2-specific CD4+ and CD8+ T-cell responses have been detected and characterized not only in COVID-19 patients and convalescents, but also unexposed individuals. Here, we review the phenotypes and functions of SARS-CoV-2-specific T cells in COVID-19 patients and the relationships between SARS-CoV-2-specific T-cell responses and COVID-19 severity. In addition, we describe the phenotypes and functions of SARS-CoV-2-specific memory T cells after recovery from COVID-19 and discuss the presence of SARS-CoV-2-reactive T cells in unexposed individuals and SARS-CoV-2-specific T-cell responses elicited by COVID-19 vaccines. A better understanding of T-cell responses is important for effective control of the current COVID-19 pandemic.
Keywords
COVID-19; SARS-CoV-2; T cell; vaccine;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Sekine, T., Perez-Potti, A., Rivera-Ballesteros, O., Stralin, K., Gorin, J.B., Olsson, A., Llewellyn-Lacey, S., Kamal, H., Bogdanovic, G., Muschiol, S., et al. (2020). Robust T cell immunity in convalescent individuals with asymptomatic or mild COVID-19. Cell 183, 158-168.e14.   DOI
2 Wilk, A.J., Rustagi, A., Zhao, N.Q., Roque, J., Martinez-Colon, G.J., McKechnie, J.L., Ivison, G.T., Ranganath, T., Vergara, R., Hollis, T., et al. (2020). A single-cell atlas of the peripheral immune response in patients with severe COVID-19. Nat. Med. 26, 1070-1076.   DOI
3 Zhuang, Z., Lai, X., Sun, J., Chen, Z., Zhang, Z., Dai, J., Liu, D., Li, Y., Li, F., Wang, Y., et al. (2021). Mapping and role of T cell response in SARS-CoV-2-infected mice. J. Exp. Med. 218, e20202187.   DOI
4 Kuri-Cervantes, L., Pampena, M.B., Meng, W., Rosenfeld, A.M., Ittner, C.A.G., Weisman, A.R., Agyekum, R.S., Mathew, D., Baxter, A.E., Vella, L.A., et al. (2020). Comprehensive mapping of immune perturbations associated with severe COVID-19. Sci. Immunol. 5, eabd7114.   DOI
5 Mateus, J., Grifoni, A., Tarke, A., Sidney, J., Ramirez, S.I., Dan, J.M., Burger, Z.C., Rawlings, S.A., Smith, D.M., Phillips, E., et al. (2020). Selective and cross-reactive SARS-CoV-2 T cell epitopes in unexposed humans. Science 370, 89-94.   DOI
6 Diao, B., Wang, C., Tan, Y., Chen, X., Liu, Y., Ning, L., Chen, L., Li, M., Liu, Y., Wang, G., et al. (2020). Reduction and functional exhaustion of T cells in patients with coronavirus disease 2019 (COVID-19). Front. Immunol. 11, 827.   DOI
7 Dan, J.M., Mateus, J., Kato, Y., Hastie, K.M., Yu, E.D., Faliti, C.E., Grifoni, A., Ramirez, S.I., Haupt, S., Frazier, A., et al. (2021). Immunological memory to SARS-CoV-2 assessed for up to 8 months after infection. Science 371, eabf4063.   DOI
8 Singer, M., Wang, C., Cong, L., Marjanovic, N.D., Kowalczyk, M.S., Zhang, H., Nyman, J., Sakuishi, K., Kurtulus, S., Gennert, D., et al. (2016). A distinct gene module for dysfunction uncoupled from activation in tumor-infiltrating T cells. Cell 166, 1500-1511.e9.   DOI
9 Agerer, B., Koblischke, M., Gudipati, V., Montano-Gutierrez, L.F., Smyth, M., Popa, A., Genger, J.W., Endler, L., Florian, D.M., Muhlgrabner, V., et al. (2021). SARS-CoV-2 mutations in MHC-I-restricted epitopes evade CD8(+) T cell responses. Sci. Immunol. 6, eabg6461.   DOI
10 Bacher, P., Rosati, E., Esser, D., Martini, G.R., Saggau, C., Schiminsky, E., Dargvainiene, J., Schroder, I., Wieters, I., Khodamoradi, Y., et al. (2020). Low-avidity CD4(+) T cell responses to SARS-CoV-2 in unexposed individuals and humans with severe COVID-19. Immunity 53, 1258-1271.e5.   DOI
11 Gattinoni, L., Lugli, E., Ji, Y., Pos, Z., Paulos, C.M., Quigley, M.F., Almeida, J.R., Gostick, E., Yu, Z., Carpenito, C., et al. (2011). A human memory T cell subset with stem cell-like properties. Nat. Med. 17, 1290-1297.   DOI
12 De Biasi, S., Meschiari, M., Gibellini, L., Bellinazzi, C., Borella, R., Fidanza, L., Gozzi, L., Iannone, A., Lo Tartaro, D., Mattioli, M., et al. (2020). Marked T cell activation, senescence, exhaustion and skewing towards TH17 in patients with COVID-19 pneumonia. Nat. Commun. 11, 3434.   DOI
13 Akondy, R.S., Fitch, M., Edupuganti, S., Yang, S., Kissick, H.T., Li, K.W., Youngblood, B.A., Abdelsamed, H.A., McGuire, D.J., Cohen, K.W., et al. (2017). Origin and differentiation of human memory CD8 T cells after vaccination. Nature 552, 362-367.   DOI
14 Anderson, E.J., Rouphael, N.G., Widge, A.T., Jackson, L.A., Roberts, P.C., Makhene, M., Chappell, J.D., Denison, M.R., Stevens, L.J., Pruijssers, A.J., et al. (2020). Safety and immunogenicity of SARS-CoV-2 mRNA-1273 vaccine in older adults. N. Engl. J. Med. 383, 2427-2438.   DOI
15 Bodewes, R., Kreijtz, J.H., and Rimmelzwaan, G.F. (2009). Yearly influenza vaccinations: a double-edged sword? Lancet Infect. Dis. 9, 784-788.   DOI
16 Ewer, K.J., Barrett, J.R., Belij-Rammerstorfer, S., Sharpe, H., Makinson, R., Morter, R., Flaxman, A., Wright, D., Bellamy, D., Bittaye, M., et al. (2021). T cell and antibody responses induced by a single dose of ChAdOx1 nCoV-19 (AZD1222) vaccine in a phase 1/2 clinical trial. Nat. Med. 27, 270-278.   DOI
17 Gattinoni, L., Speiser, D.E., Lichterfeld, M., and Bonini, C. (2017). T memory stem cells in health and disease. Nat. Med. 23, 18-27.   DOI
18 Braun, J., Loyal, L., Frentsch, M., Wendisch, D., Georg, P., Kurth, F., Hippenstiel, S., Dingeldey, M., Kruse, B., Fauchere, F., et al. (2020). SARS-CoV-2-reactive T cells in healthy donors and patients with COVID-19. Nature 587, 270-274.   DOI
19 Zuo, J., Dowell, A.C., Pearce, H., Verma, K., Long, H.M., Begum, J., Aiano, F., Amin-Chowdhury, Z., Hallis, B., Stapley, L., et al. (2021). Robust SARS-CoV-2-specific T cell immunity is maintained at 6 months following primary infection. Nat. Immunol. 22, 620-626.   DOI
20 Fuertes Marraco, S.A., Soneson, C., Cagnon, L., Gannon, P.O., Allard, M., Abed Maillard, S., Montandon, N., Rufer, N., Waldvogel, S., Delorenzi, M., et al. (2015). Long-lasting stem cell-like memory CD8+ T cells with a naive-like profile upon yellow fever vaccination. Sci. Transl. Med. 7, 282ra248.
21 Ge, X., Tan, V., Bollyky, P.L., Standifer, N.E., James, E.A., and Kwok, W.W. (2010). Assessment of seasonal influenza A virus-specific CD4 T-cell responses to 2009 pandemic H1N1 swine-origin influenza A virus. J. Virol. 84, 3312-3319.   DOI
22 Huang, C., Wang, Y., Li, X., Ren, L., Zhao, J., Hu, Y., Zhang, L., Fan, G., Xu, J., Gu, X., et al. (2020). Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 395, 497-506.   DOI
23 Kim, J., Chang, D.Y., Lee, H.W., Lee, H., Kim, J.H., Sung, P.S., Kim, K.H., Hong, S.H., Kang, W., Lee, J., et al. (2018). Innate-like cytotoxic function of bystander-activated CD8(+) T cells is associated with liver injury in acute hepatitis A. Immunity 48, 161-173.e5.   DOI
24 Zheng, H.Y., Zhang, M., Yang, C.X., Zhang, N., Wang, X.C., Yang, X.P., Dong, X.Q., and Zheng, Y.T. (2020a). Elevated exhaustion levels and reduced functional diversity of T cells in peripheral blood may predict severe progression in COVID-19 patients. Cell. Mol. Immunol. 17, 541-543.   DOI
25 Zhou, R., To, K.K., Wong, Y.C., Liu, L., Zhou, B., Li, X., Huang, H., Mo, Y., Luk, T.Y., Lau, T.T., et al. (2020). Acute SARS-CoV-2 infection impairs dendritic cell and T cell responses. Immunity 53, 864-877.e5.   DOI
26 Keech, C., Albert, G., Cho, I., Robertson, A., Reed, P., Neal, S., Plested, J.S., Zhu, M., Cloney-Clark, S., Zhou, H., et al. (2020). Phase 1-2 trial of a SARS-CoV-2 recombinant spike protein nanoparticle vaccine. N. Engl. J. Med. 383, 2320-2332.   DOI
27 Kusnadi, A., Ramirez-Suastegui, C., Fajardo, V., Chee, S.J., Meckiff, B.J., Simon, H., Pelosi, E., Seumois, G., Ay, F., Vijayanand, P., et al. (2021). Severely ill COVID-19 patients display impaired exhaustion features in SARS-CoV-2-reactive CD8(+) T cells. Sci. Immunol. 6, eabe4782.   DOI
28 Lee, J.S., Park, S., Jeong, H.W., Ahn, J.Y., Choi, S.J., Lee, H., Choi, B., Nam, S.K., Sa, M., Kwon, J.S., et al. (2020). Immunophenotyping of COVID-19 and influenza highlights the role of type I interferons in development of severe COVID-19. Sci. Immunol. 5, eabd1554.   DOI
29 Grifoni, A., Weiskopf, D., Ramirez, S.I., Mateus, J., Dan, J.M., Moderbacher, C.R., Rawlings, S.A., Sutherland, A., Premkumar, L., Jadi, R.S., et al. (2020). Targets of T cell responses to SARS-CoV-2 coronavirus in humans with COVID-19 disease and unexposed individuals. Cell 181, 1489-1501.e15.   DOI
30 Chen, R.E., Zhang, X., Case, J.B., Winkler, E.S., Liu, Y., VanBlargan, L.A., Liu, J., Errico, J.M., Xie, X., Suryadevara, N., et al. (2021). Resistance of SARS-CoV-2 variants to neutralization by monoclonal and serum-derived polyclonal antibodies. Nat. Med. 27, 717-726.   DOI
31 Sagar, M., Reifler, K., Rossi, M., Miller, N.S., Sinha, P., White, L.F., and Mizgerd, J.P. (2021). Recent endemic coronavirus infection is associated with less-severe COVID-19. J. Clin. Invest. 131, e143380.   DOI
32 Ng, O.W., Chia, A., Tan, A.T., Jadi, R.S., Leong, H.N., Bertoletti, A., and Tan, Y.J. (2016). Memory T cell responses targeting the SARS coronavirus persist up to 11 years post-infection. Vaccine 34, 2008-2014.   DOI
33 Ni, L., Ye, F., Cheng, M.L., Feng, Y., Deng, Y.Q., Zhao, H., Wei, P., Ge, J., Gou, M., Li, X., et al. (2020). Detection of SARS-CoV-2-specific humoral and cellular immunity in COVID-19 convalescent individuals. Immunity 52, 971-977.e3.   DOI
34 Peng, Y., Mentzer, A.J., Liu, G., Yao, X., Yin, Z., Dong, D., Dejnirattisai, W., Rostron, T., Supasa, P., Liu, C., et al. (2020). Broad and strong memory CD4(+) and CD8(+) T cells induced by SARS-CoV-2 in UK convalescent individuals following COVID-19. Nat. Immunol. 21, 1336-1345.   DOI
35 Rehermann, B. and Shin, E.C. (2005). Private aspects of heterologous immunity. J. Exp. Med. 201, 667-670.   DOI
36 Rha, M.S., Jeong, H.W., Ko, J.H., Choi, S.J., Seo, I.H., Lee, J.S., Sa, M., Kim, A.R., Joo, E.J., Ahn, J.Y., et al. (2021). PD-1-expressing SARS-CoV-2-specific CD8(+) T cells are not exhausted, but functional in patients with COVID-19. Immunity 54, 44-52.e3.   DOI
37 Rodda, L.B., Netland, J., Shehata, L., Pruner, K.B., Morawski, P.A., Thouvenel, C.D., Takehara, K.K., Eggenberger, J., Hemann, E.A., Waterman, H.R., et al. (2021). Functional SARS-CoV-2-specific immune memory persists after mild COVID-19. Cell 184, 169-183.e17.   DOI
38 Rydyznski Moderbacher, C., Ramirez, S.I., Dan, J.M., Grifoni, A., Hastie, K.M., Weiskopf, D., Belanger, S., Abbott, R.K., Kim, C., Choi, J., et al. (2020). Antigen-specific adaptive immunity to SARS-CoV-2 in acute COVID-19 and associations with age and disease severity. Cell 183, 996-1012.e19.   DOI
39 Sattler, A., Angermair, S., Stockmann, H., Heim, K.M., Khadzhynov, D., Treskatsch, S., Halleck, F., Kreis, M.E., and Kotsch, K. (2020). SARS-CoV-2-specific T cell responses and correlations with COVID-19 patient predisposition. J. Clin. Invest. 130, 6477-6489.   DOI
40 Song, J.W., Zhang, C., Fan, X., Meng, F.P., Xu, Z., Xia, P., Cao, W.J., Yang, T., Dai, X.P., Wang, S.Y., et al. (2020). Immunological and inflammatory profiles in mild and severe cases of COVID-19. Nat. Commun. 11, 3410.   DOI
41 Tan, A.T., Linster, M., Tan, C.W., Le Bert, N., Chia, W.N., Kunasegaran, K., Zhuang, Y., Tham, C.Y.L., Chia, A., Smith, G.J.D., et al. (2021). Early induction of functional SARS-CoV-2-specific T cells associates with rapid viral clearance and mild disease in COVID-19 patients. Cell Rep. 34, 108728.   DOI
42 Le Bert, N., Tan, A.T., Kunasegaran, K., Tham, C.Y.L., Hafezi, M., Chia, A., Chng, M.H.Y., Lin, M., Tan, N., Linster, M., et al. (2020). SARS-CoV-2-specific T cell immunity in cases of COVID-19 and SARS, and uninfected controls. Nature 584, 457-462.   DOI
43 Gregorova, M., Morse, D., Brignoli, T., Steventon, J., Hamilton, F., Albur, M., Arnold, D., Thomas, M., Halliday, A., Baum, H., et al. (2020). Post-acute COVID-19 associated with evidence of bystander T-cell activation and a recurring antibiotic-resistant bacterial pneumonia. Elife 9, e63430.   DOI
44 Jung, J.H., Rha, M.S., Sa, M.A., Choi, H.K., Jeon, J.H., Seok, H.R., Park, D.W., Park, S.H., Jeong, H.W., Choi, W.S., et al. (2021). SARS-CoV-2-specific T cell memory is sustained in COVID-19 convalescents for 8 months with successful development of stem cell-like memory T cells. MedRxiv, https://doi.org/10.1101/2021.03.04.21252658
45 Kim, T.S. and Shin, E.C. (2019). The activation of bystander CD8(+) T cells and their roles in viral infection. Exp. Mol. Med. 51, 1-9.
46 Liao, M., Liu, Y., Yuan, J., Wen, Y., Xu, G., Zhao, J., Cheng, L., Li, J., Wang, X., Wang, F., et al. (2020). Single-cell landscape of bronchoalveolar immune cells in patients with COVID-19. Nat. Med. 26, 842-844.   DOI
47 Mathew, D., Giles, J.R., Baxter, A.E., Oldridge, D.A., Greenplate, A.R., Wu, J.E., Alanio, C., Kuri-Cervantes, L., Pampena, M.B., D'Andrea, K., et al. (2020). Deep immune profiling of COVID-19 patients reveals distinct immunotypes with therapeutic implications. Science 369, eabc8511.   DOI
48 McMahan, K., Yu, J., Mercado, N.B., Loos, C., Tostanoski, L.H., Chandrashekar, A., Liu, J., Peter, L., Atyeo, C., Zhu, A., et al. (2021). Correlates of protection against SARS-CoV-2 in rhesus macaques. Nature 590, 630-634.   DOI
49 Merad, M. and Martin, J.C. (2020). Pathological inflammation in patients with COVID-19: a key role for monocytes and macrophages. Nat. Rev. Immunol. 20, 355-362.   DOI
50 Rothman, A.L. (2011). Immunity to dengue virus: a tale of original antigenic sin and tropical cytokine storms. Nat. Rev. Immunol. 11, 532-543.   DOI
51 Wang, Z., Schmidt, F., Weisblum, Y., Muecksch, F., Barnes, C.O., Finkin, S., Schaefer-Babajew, D., Cipolla, M., Gaebler, C., Lieberman, J.A., et al. (2021b). mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants. Nature 592, 616-622.   DOI
52 Tang, F., Quan, Y., Xin, Z.T., Wrammert, J., Ma, M.J., Lv, H., Wang, T.B., Yang, H., Richardus, J.H., Liu, W., et al. (2011). Lack of peripheral memory B cell responses in recovered patients with severe acute respiratory syndrome: a six-year follow-up study. J. Immunol. 186, 7264-7268.   DOI
53 Wang, P., Nair, M.S., Liu, L., Iketani, S., Luo, Y., Guo, Y., Wang, M., Yu, J., Zhang, B., Kwong, P.D., et al. (2021a). Antibody resistance of SARS-CoV-2 variants B.1.351 and B.1.1.7. Nature 593, 130-135.   DOI
54 Wherry, E.J. and Kurachi, M. (2015). Molecular and cellular insights into T cell exhaustion. Nat. Rev. Immunol. 15, 486-499.   DOI
55 Zhao, J., Alshukairi, A.N., Baharoon, S.A., Ahmed, W.A., Bokhari, A.A., Nehdi, A.M., Layqah, L.A., Alghamdi, M.G., Al Gethamy, M.M., Dada, A.M., et al. (2017). Recovery from the Middle East respiratory syndrome is associated with antibody and T-cell responses. Sci. Immunol. 2, eaan5393.   DOI
56 Welsh, R.M., Che, J.W., Brehm, M.A., and Selin, L.K. (2010). Heterologous immunity between viruses. Immunol. Rev. 235, 244-266.   DOI
57 Sette, A. and Crotty, S. (2020). Pre-existing immunity to SARS-CoV-2: the knowns and unknowns. Nat. Rev. Immunol. 20, 457-458.   DOI
58 Sridhar, S., Begom, S., Bermingham, A., Hoschler, K., Adamson, W., Carman, W., Bean, T., Barclay, W., Deeks, J.J., and Lalvani, A. (2013). Cellular immune correlates of protection against symptomatic pandemic influenza. Nat. Med. 19, 1305-1312.   DOI
59 Tarke, A., Sidney, J., Methot, N., Zhang, Y., Dan, J.M., Goodwin, B., Rubiro, P., Sutherland, A., da Silva Antunes, R., Frazier, A., et al. (2021). Negligible impact of SARS-CoV-2 variants on CD4 (+) and CD8 (+) T cell reactivity in COVID-19 exposed donors and vaccinees. BioRxiv, https://doi.org/10.1101/2021.02.27.433180
60 Wilkinson, T.M., Li, C.K., Chui, C.S., Huang, A.K., Perkins, M., Liebner, J.C., Lambkin-Williams, R., Gilbert, A., Oxford, J., Nicholas, B., et al. (2012). Preexisting influenza-specific CD4+ T cells correlate with disease protection against influenza challenge in humans. Nat. Med. 18, 274-280.   DOI
61 Zheng, M., Gao, Y., Wang, G., Song, G., Liu, S., Sun, D., Xu, Y., and Tian, Z. (2020b). Functional exhaustion of antiviral lymphocytes in COVID-19 patients. Cell. Mol. Immunol. 17, 533-535.   DOI
62 Sahin, U., Muik, A., Derhovanessian, E., Vogler, I., Kranz, L.M., Vormehr, M., Baum, A., Pascal, K., Quandt, J., Maurus, D., et al. (2020). COVID-19 vaccine BNT162b1 elicits human antibody and TH1 T cell responses. Nature 586, 594-599.   DOI
63 Nelde, A., Bilich, T., Heitmann, J.S., Maringer, Y., Salih, H.R., Roerden, M., Lubke, M., Bauer, J., Rieth, J., Wacker, M., et al. (2021). SARS-CoV-2-derived peptides define heterologous and COVID-19-induced T cell recognition. Nat. Immunol. 22, 74-85.   DOI