SARS-CoV-2-Specific T Cells Exhibit Phenotypic Features of Helper Function, Lack of Terminal Differentiation, and High Proliferation Potential

Abstract

Convalescing coronavirus disease 2019 (COVID-19) patients mount robust T cell responses against SARS-CoV-2, suggesting an important role of T cells in viral clearance. To date, the phenotypes of SARS-CoV-2-specific T cells remain poorly defined. Using 38-parameter CyTOF, we phenotyped longitudinal specimens of SARS-CoV-2-specific CD4+ and CD8+ T cells from nine individuals who recovered from mild COVID-19. SARS-CoV-2-specific CD4+ T cells were exclusively Th1 cells and predominantly Tcm cells with phenotypic features of robust helper function. SARS-CoV-2-specific CD8+ T cells were predominantly Temra cells in a state of less terminal differentiation than most Temra cells. Subsets of SARS-CoV-2-specific T cells express CD127, can proliferate homeostatically, and can persist for over 2 months. Our results suggest that long-lived and robust T cell immunity is generated following natural SARS-CoV-2 infection and support an important role of SARS-CoV-2-specific T cells in host control of COVID-19.

Post-acute COVID-19 associated with evidence of bystander T-cell activation and a recurring antibiotic-resistant bacterial pneumonia

“…CMV and spike 1-specific CD4+ T cells were mainly contained respectively within the TEM and the TEM/TCM subsets, while CMV and spike 1-specific CD8+ T cells were mainly contained respectively within the TEMRA and the TEM subsets. The predominant TEMRA phenotype of SARS-CoV-2 specific CD8+ T-cells in convalescent COVID patients is in line with recent work ( Neidleman et al, 2020 ). The presence of a large proportion of CD8+ TEMRA within the CMV and spike 1-specific CD8+ T cell populations also supports the notion that these cells are stimulated through cytokine receptors rather than through the TCR, as TEMRA cells are believed to arise following antigen withdrawal and cytokine-mediated stimulation (for e.g.…”

T cell immunity to SARS-CoV-2 following natural infection and vaccination

“…Additionally, production of IFN-γ, TNF-α, GzmB and/or surface expression of the CD107a marker of degranulation has been detected in CD8 + T cells [ 31 , 43 ], with one report demonstrating higher levels of cytotoxicity markers in severe cases [ 66 ]. In contrast to mild cases [ 57 ] however, evidence of type 2 (IL-5, IL-13, IL-9, and IL-10) and type 3 (IL-17A, IL-17F, and IL-22) responses in more severe COVID-19 was found in some [ 23 , 31 , 32 ], but not in all reports [ 48 ]. These responses may contribute to the production of IL-1β, IL-6, CXCL8/IL-8, TNF, and CXCL10/IP-10, which are associated with inflammation, organ damage, T cell impairment, and neutrophilia [ 34 , 67 , 68 ].…”

“…The majority of current data suggests that although both T cell subsets can acquire central memory (T CM ), effector memory (T EM ), and stem cell-like memory (T SCM ) phenotypes, there is a CD4 + T cell bias towards T CM , and CD8 + T cells towards T EM , with heterogeneity in differentiation status [ 23 , 26 , 31 , 43 , 45 , 52 , 57 , 58 ]. In studies of mild to severe COVID-19 [ 31 , 57 , 58 ], CD8 + T EM/TEMRA cells appeared to be less differentiated compared to critical cases, including those with acute respiratory distress syndrome (ARDS) [ 23 , 45 ]. Studies directly comparing different stages of infection and recovery across the disease spectrum would inform understanding of the elicitation, phenotype, kinetics, and longevity of SARS-CoV-2-specific T cells, and importantly, how they might influence the response to reinfection.…”

“…Virus-specific T FH are compulsory for the development of affinity-matured neutralizing antibodies. Phenotypic analyses of CD4 + T cells from COVID-19 patients have revealed the heterogeneity of circulating T FH (cT FH ) (CXCR5 + PD-1 + ) [ 26 , 31 , 34 , 35 , 48 , 51 , 57 , 59 , 72 ]. In convalescent mild to moderate COVID-19, although S-specific cT FH were enriched for T H 17-like (CCR6 + CXCR3 - ) cells, T H 1/2-like (CCR6 − CXCR3 +/− ) cells were associated with the highest plasma neutralizing activity [ 72 ].…”

A 21st Century Evil: Immunopathology and New Therapies of COVID-19

“…When symptomatic individuals were stratified according to the severity of the disease, those with moderate to severe conditions had higher levels of IL-7. In addition, SARS-CoV-2-specific T cells from the peripheral blood of convalescent individuals of COVID-19 show high expressions of CD127, a receptor necessary for homeostatic cell proliferation triggered by IL-7, which may be related to the recovery observed (157). Patients with a severe COVID-19 condition, on the other hand, have an increased IL-7 production, but contradictorily they also have severe lymphopenia.…”