Heterogenous CD8+ T Cell Maturation and ‘Polarization’ in Acute and Convalescent COVID-19 Patients

Abstract

Background. The adaptive antiviral immune response requires interaction between CD8+ T cells, dendritic cells, and Th1 cells for controlling SARS-CoV-2 infection, but the data regarding the role of CD8+ T cells in the acute phase of COVID-19 and post-COVID-19 syndrome are still limited. Methods.. Peripheral blood samples collected from patients with acute COVID-19 (n = 71), convalescent subjects bearing serum SARS-CoV-2 N-protein-specific IgG antibodies (n = 51), and healthy volunteers with no detectable antibodies to any SARS-CoV-2 proteins (HC, n = 46) were analyzed using 10-color flow cytometry. Results. Patients with acute COVID-19 vs. HC and COVID-19 convalescents showed decreased absolute numbers of CD8+ T cells, whereas the frequency of CM and TEMRA CD8+ T cells in acute COVID-19 vs. HC was elevated. COVID-19 convalescents vs. HC had increased naïve and CM cells, whereas TEMRA cells were decreased compared to HC. Cell-surface CD57 was highly expressed by the majority of CD8+ T cells subsets during acute COVID-19, but convalescents had increased CD57 on ‘naïve’, CM, EM4, and pE1 2–3 months post-symptom onset. CXCR5 expression was altered in acute and convalescent COVID-19 subjects, whereas the frequencies of CXCR3+ and CCR4+ cells were decreased in both patient groups vs. HC. COVID-19 convalescents had increased CCR6-expressing CD8+ T cells. Moreover, CXCR3+CCR6- Tc1 cells were decreased in patients with acute COVID-19 and COVID-19 convalescents, whereas Tc2 and Tc17 levels were increased compared to HC. Finally, IL-27 negatively correlated with the CCR6+ cells in acute COVID-19 patients. Conclusions. We described an abnormal CD8+ T cell profile in COVID-19 convalescents, which resulted in lower frequencies of effector subsets (TEMRA and Tc1), higher senescent state (upregulated CD57 on ‘naïve’ and memory cells), and higher frequencies of CD8+ T cell subsets expressing lung tissue and mucosal tissue homing molecules (Tc2, Tc17, and Tc17.1). Thus, our data indicate that COVID-19 can impact the long-term CD8+ T cell immune response.

The role of cholesterol metabolism in predicting clinical outcome of patients with severe COVID-19

“…However, secretion of IL-15 and IL-27 was increased in non-survivors compared to both survived patients and controls that is consistent with previously published data [32]. It is interesting to note that IL-15 and IL-27 are early cytokines, and this change in their concentration indicates the activation of the innate immune response when the virus is recognized by the epithelial or dendritic cells of the body, followed by the induction of the innate defense of body and induction of inflammation processes [31,[33][34]. In accordance with our and previous data, IL-15, IL-27 were previously associated with the severity and fatal outcome of COVID-19 [32,[35][36][37][38].…”

“…Increased secretion of CCL20/MIP3ɑ is a new finding in COVID-19, although we previously reported an increase in concentrations of other macrophage inflammatory proteins, CCL3/MIP-1a and CCL4/MIP-1b [30]. CCL20/MIP3ɑ mainly elicits its effector function via CCR6 receptor binding; interestingly enough, we previously noted a negative correlation between CCR6 ex-pressing CD8+ cells and IL-27 [31]. However, secretion of IL-15 and IL-27 was increased in non-survivors compared to both survived patients and controls that is consistent with previously published data [32].…”

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“…For example, Th17 hyperactivation and disturbances in their subpopulation composition, changes in the ratio of “regulatory” and “pro-inflammatory” Tfh cells as well as a decrease in the control of antibody-producing B cells are very similar to changes, characteristic of a wide range of autoimmune pathologies [ 122 , 123 ], the incidence of which increases sharply after COVID-19 [ 124 ]. Long-term disturbances in the processes of maturation and differentiation of NK-cells and cytotoxic T-lymphocytes, the presence of inhibitory receptors or markers of “cellular aging” on their surface which is accompanied, first of all, by low efficiency of destruction of target cells may reduce the effectiveness of antitumor and antiviral immunity [ 125 , 126 , 127 ]. In addition, hyperactivation of tissue macrophages, the formation of a pool of activated monocytes migrating from the bloodstream against the background of a cytokine “storm” and a change in the balance between T-helpers of different populations (Th1/Th2 and Th17/Treg) in the focus of inflammation contribute to the disruption of the regeneration of inflamed tissue of different localization and development of fibrosis [ 128 , 129 ].…”

Regulated Arginine Metabolism in Immunopathogenesis of a Wide Range of Diseases: Is There a Way to Pass between Scylla and Charybdis?

“…The patient’s T cell level in the circulation was reduced both in comparison with control group and COVID-19 convalescent patients [ 170 , 171 , 172 ]. A dynamic T cell reduction as well as CD3+ CD4+ and CD3+ CD8+ cells was characteristic of patients with severe vs. moderate disease course [ 173 , 174 ], and the subset profile of both CD4+ and CD8+ T-lymphocytes underwent dramatic changes [ 175 , 176 ]. The detected alterations in T cell differentiation and “polarization” could, among others, be associated with alteration in relevant proliferative activity [ 177 ]; however, at least in vitro, supplementation with additional L-Arg restored CD3+ cell proliferative potential [ 161 ].…”