Definition der zytotoxischen T-Zell-Antwort bei COVID-19-Patienten
Virologie
Zusammenfassung der Projektergebnisse
The population of cytotoxic T cells is responsible for the elimination of infected cells and tumors. However, the enhanced activity of these cells may lead to inflammation in infected organs and to severe pathology. The optimal functional regulation of cytotoxic cells is a critical requirement for the balance between virus control and side effects during cytotoxic immune responses. In our current project we started with an analysis of cytotoxic T cells and NK cells during acute SARS-CoV-2 infection of patients that were hospitalized due to COVID-19. During the investigation, we observed an association between cytotoxic T cell responses and Macrophage Migration Inhibitory Factor (MIF) production as well as the expression of receptors for MIF on cytotoxic T cells. MIF holds a variety of functions, including enzymatic activity such as tautomerase, proinflammatory action by recruitment of inflammatory cells to sites of tissue damage, or counter-regulation of immunosuppressive glucocorticoids. In different inflammatory diseases, levels of circulating MIF are elevated, suggesting a major involvement of MIF in disease development and course. Nevertheless, the role of MIF and whether it has beneficial or detrimental effects in SARS-CoV-2 infections remains elusive. The main cellular receptor for MIF is CD74. CD74 has no intracellular signaling domain, so it is dependent on complexing with its co-receptors CD44, CXCR2, or CXCR4 in order to induce intracellular signaling. The cell-specific surface expression of the MIF receptor and its coreceptors thus represents the cell’s responsiveness to MIF. While CD74 is mainly expressed on MHCII+ antigen-presenting cells, it can also be found on other cells derived from hematopoietic lineages, such as T cells. We observed: The enhancement of MIF and its soluble receptor sCD74 inin the plasma of COVID-19 patients. This data proposes the possible regulatory effects of MIF on T cell responses. Association of COVID-19 with enhanced expression of the MIF receptor CD74 on CD4+ and CD8+ T cells in the group of severely ill COVID-19 patients. All CD74+ T cells constitutively expressed CD44 and SARS-CoV-2 enhanced the expression of CXCR2 and CXCR4 co-receptors. The convCD4+ T cells, but not Tregs enhanced expression of CD74 and coreceptor molecules during COVID-19. SARS-CoV-2 leads to a reduction of CD44 and enhancement of CXCR2 and CXCR on convCD4+ T cells with a memory phenotype. CD8+ T cells showed enhanced CD74 expression during SARS-CoV-2 infection. All CD74+ CD8+ T cells constitutively expressed CD44 and an enhanced expression of CXCR2 was found. CD74+ T cells more frequently produce cytotoxic molecules in comparison to CD74- T cells from COVID-19 patients. For CD8+ T cells, the CD74 molecule in combination with differentiation markers may be suitable as a marker of cytotoxic effector CD8+ T cells.
Projektbezogene Publikationen (Auswahl)
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Analysis of the Long-Term Impact on Cellular Immunity in COVID-19-Recovered Individuals Reveals a Profound NKT Cell Impairment. mBio, 12(2).
Liu, Jia; Yang, Xuecheng; Wang, Hua; Li, Ziwei; Deng, Hui; Liu, Jing; Xiong, Shue; He, Junyi; Feng, Xuemei; Guo, Chunxia; Wang, Weixian; Zelinskyy, Gennadiy; Trilling, Mirko; Sutter, Kathrin; Senff, Tina; Menne, Christopher; Timm, Joerg; Zhang, Yanfang; Deng, Fei ... & Zheng, Xin
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Characterization of SARS-CoV-2-Specific Humoral and Cellular Immune Responses Induced by Inactivated COVID-19 Vaccines in a Real-World Setting. Frontiers in Immunology, 12.
Li, Ziwei; Xiang, Tiandan; Liang, Boyun; Deng, Hui; Wang, Hua; Feng, Xuemei; Quan, Xufeng; Wang, Xiaoyan; Li, Sumeng; Lu, Sihong; Yang, Xuecheng; Wang, Baoju; Zelinskyy, Gennadiy; Trilling, Mirko; Sutter, Kathrin; Lu, Mengji; Dittmer, Ulf; Yang, Dongliang; Zheng, Xin & Liu, Jia
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SARS‐CoV‐2‐specific humoral and cellular immunity in two renal transplants and two hemodialysis patients treated with convalescent plasma. Journal of Medical Virology, 93(5), 3047-3054.
Lindemann, Monika; Krawczyk, Adalbert; Dolff, Sebastian; Konik, Margarethe; Rohn, Hana; Platte, Maximillian; Thümmler, Laura; Schwarzkopf, Sina; Schipper, Leonie; Bormann, Maren; van de Sand, Lukas; Breyer, Marianne; Klump, Hannes; Knop, Dietmar; Lenz, Veronika; Temme, Christian; Dittmer, Ulf; Horn, Peter A. & Witzke, Oliver
