However, cases of reinfection have been reported ( 22), raising questions on the clinical significance of T-cell polarization and peptide repertoire specificities against current viral variants.
Memory Th1/Tc1 T cells specific for SARS-CoV-2 and follicular T helper (Tfh) cells have been detected in mild cases ( 21). They are mainly directed against spike, membrane, and NC proteins and have been studied in greater detail by single-cell sequencing in a limited number of patients ( 21). Indeed, functional T-cell responses remain increased in both frequency and intensity up to six months postinfection ( 5). SARS-CoV-2–specific T-cell immunity plays a key role during acute COVID-19 and up to eight months after convalescence ( 16–20). Naïve T-cell differentiation to distinct Th fates is guided by inputs integrated from TCR affinity, CD25 expression, costimulatory molecules, and cytokines ( 15). In contrast, Th2 (and Tc2) cells produce IL4, IL5, IL10, and IL13, providing optimal help for both humoral responses and mucosal immunity, through the production of mast cell and eosinophil growth and differentiation factors, thus contributing to antiparasitic and allergic reactions. Therefore, Th1/Tc1 cells drive the phagocyte-dependent host response and are pivotal for antiviral responses ( 13, 14). Th1 cells (as well as cytotoxic T cells with a similar cytokine pattern, referred to as Tc1 cells) produce IFNγ, IL2, and TNFα as well as promote macrophage activation, antibody-dependent cell cytotoxicity, delayed type hypersensitivity, and opsonizing and complement-fixing IgG2a antibody production ( 12). The Th1 versus Th2 concept suggests that modulation of the relative contribution of Th1 or Th2 cytokines regulates the balance between immune protection against microbes and immunopathology ( 12–14). We speculate that the next generation of vaccines should elicit Th1/Tc1 T-cell responses against the S1-RBD domain of emerging viral variants. Current vaccines triggered Th1/Tc1 responses in only a fraction of all subject categories, more effectively against the original sequence of S1-RBD than that from viral variants. Individuals susceptible to infection exhibited a specific deficit in the T helper 1/T cytotoxic 1 (Th1/Tc1) peptide repertoire affecting the receptor binding domain of the spike protein (S1-RBD), a hotspot of viral mutations. A disbalance between type 1 and 2 cytokine release was associated with high susceptibility to COVID-19. We characterized the polarity and specificity of memory T cells directed against SARS-CoV-2 viral lysates and peptides to determine correlates with spontaneous, virus-elicited, or vaccine-induced protection against COVID-19 in disease-free and cancer-bearing individuals. Vaccination against coronavirus disease 2019 (COVID-19) relies on the in-depth understanding of protective immune responses to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2).
Chevalier, Sophie Caillat-Zucman, Florence Fenollar, Emma Guttman-Yassky, Odile Launay, Guido Kroemer, Bernard La Scola, Markus Maeurer, Lisa Derosa, Laurence Zitvogel The Polarity and Specificity of Antiviral T Lymphocyte Responses Determine Susceptibility to SARS-CoV-2 Infection in Patients with Cancer and Healthy Individuals. Lérias, Ariane Laparra, Alice Bernard-Tessier, Benoît Kloeckner, Marianne Gazzano, François-Xavier Danlos, Safae Terrisse, Eugenie Pizzato, Caroline Flament, Pierre Ly, Eric Tartour, Nadine Benhamouda, Lydia Meziani, Abdelhakim Ahmed-Belkacem, Makoto Miyara, Guy Gorochov, Fabrice Barlesi, Alexandre Trubert, Benjamin Ungar, Yeriel Estrada, Caroline Pradon, Emmanuelle Gallois, Fanny Pommeret, Emeline Colomba, Pernelle Lavaud, Marc Deloger, Nathalie Droin, Eric Deutsch, Bertrand Gachot, Jean-Philippe Spano, Mansouria Merad, Florian Scotté, Aurélien Marabelle, Frank Griscelli, Jean-Yves Blay, Jean-Charles Soria, Miriam Merad, Fabrice André, Juliette Villemonteix, Mathieu F. Jean-Eudes Fahrner, Imran Lahmar, Anne-Gaëlle Goubet, Yacine Haddad, Agathe Carrier, Marine Mazzenga, Damien Drubay, Carolina Alves Costa Silva, Lyon COVID Study Group, Eric de Sousa, Cassandra Thelemaque, Cléa Melenotte, Agathe Dubuisson, Arthur Geraud, Gladys Ferrere, Roxanne Birebent, Camille Bigenwald, Marion Picard, Luigi Cerbone, Joana R.