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Deprecated: Implicit conversion from float 300.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 J+Immunol 2021 ; 207 (4): 1099-1111 Nephropedia Template TP
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The Quality of SARS-CoV-2-Specific T Cell Functions Differs in Patients with Mild/Moderate versus Severe Disease, and T Cells Expressing Coinhibitory Receptors Are Highly Activated #MMPMID34312258
Shahbaz S; Xu L; Sligl W; Osman M; Bozorgmehr N; Mashhouri S; Redmond D; Perez Rosero E; Walker J; Elahi S
J Immunol 2021[Aug]; 207 (4): 1099-1111 PMID34312258show ga
Understanding the function of SARS-CoV-2 Ag-specific T cells is crucial for the monitoring of antiviral immunity and vaccine design. Currently, both impaired and robust T cell immunity is described in COVID-19 patients. In this study, we explored and compared the effector functions of SARS-CoV-2-reactive T cells expressing coinhibitory receptors and examine the immunogenicity of SARS-CoV-2 S, M, and N peptide pools in regard to specific effector T cell responses, Th1/Th2/Th17, in COVID-19 patients. Analyzing a cohort of 108 COVID-19 patients with mild, moderate, and severe disease, we observed that coinhibitory receptors (e.g., PD-1, CTLA-4, TIM-3, VISTA, CD39, CD160, 2B4, TIGIT, Gal-9, and NKG2A) were upregulated on both CD4(+) and CD8(+) T cells. Importantly, the expression of coinhibitory receptors on T cells recognizing SARS-CoV-2 peptide pools (M/N/S) was associated with increased frequencies of cytokine-producing T cells. Thus, our data refute the concept of pathological T cell exhaustion in COVID-19 patients. Despite interindividual variations in the T cell response to viral peptide pools, a Th2 phenotype was associated with asymptomatic and milder disease, whereas a robust Th17 was associated with severe disease, which may potentiate the hyperinflammatory response in patients admitted to the Intensive Care Unit. Our data demonstrate that T cells may either play a protective or detrimental role in COVID-19 patients. This finding could have important implications for immune correlates of protection, diagnostic, and prophylaxis with respect to COVID-19 management.