HCV-specific CD4+ T cells of patients with acute and chronic HCV infection display high expression of TIGIT and other co-inhibitory molecules
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HCV-specific CD4+ T cells of patients with acute and chronic HCV infection display high expression of TIGIT and other co-inhibitory molecules. / Ackermann, Christin; Smits, Maike; Woost, Robin; Eberhard, Johanna M; Peine, Sven; Kummer, Silke; Marget, Matthias; Kuntzen, Thomas; Kwok, William W; Lohse, Ansgar W; Jacobs, Thomas; Boettler, Tobias; Schulze Zur Wiesch, Julian.
in: SCI REP-UK, Jahrgang 9, Nr. 1, 23.07.2019, S. 10624.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - HCV-specific CD4+ T cells of patients with acute and chronic HCV infection display high expression of TIGIT and other co-inhibitory molecules
AU - Ackermann, Christin
AU - Smits, Maike
AU - Woost, Robin
AU - Eberhard, Johanna M
AU - Peine, Sven
AU - Kummer, Silke
AU - Marget, Matthias
AU - Kuntzen, Thomas
AU - Kwok, William W
AU - Lohse, Ansgar W
AU - Jacobs, Thomas
AU - Boettler, Tobias
AU - Schulze Zur Wiesch, Julian
PY - 2019/7/23
Y1 - 2019/7/23
N2 - The combined regulation of a network of inhibitory and activating T cell receptors may be a critical step in the development of chronic HCV infection. Ex vivo HCV MHC class I + II tetramer staining and bead-enrichment was performed with baseline and longitudinal PBMC samples of a cohort of patients with acute, chronic and spontaneously resolved HCV infection to assess the expression pattern of the co-inhibitory molecule TIGIT together with PD-1, BTLA, Tim-3, as well as OX40 and CD226 (DNAM-1) of HCV-specific CD4+ T cells, and in a subset of patients of HCV-specific CD8+ T cells. As the main result, we found a higher expression level of TIGIT+ PD-1+ on HCV-specific CD4+ T cells during acute and chronic HCV infection compared to patients with spontaneously resolved HCV infection (p < 0,0001). Conversely, expression of the complementary co-stimulatory receptor of TIGIT, CD226 (DNAM-1) was significantly decreased on HCV-specific CD4+ T cells during chronic infection. The predominant phenotype of HCV-specific CD4+ T cells during acute and chronic infection was TIGIT+, PD-1+, BTLA+, Tim-3-. This comprehensive phenotypic study confirms TIGIT together with PD-1 as a discriminatory marker of dysfunctional HCV-specific CD4+ T cells.
AB - The combined regulation of a network of inhibitory and activating T cell receptors may be a critical step in the development of chronic HCV infection. Ex vivo HCV MHC class I + II tetramer staining and bead-enrichment was performed with baseline and longitudinal PBMC samples of a cohort of patients with acute, chronic and spontaneously resolved HCV infection to assess the expression pattern of the co-inhibitory molecule TIGIT together with PD-1, BTLA, Tim-3, as well as OX40 and CD226 (DNAM-1) of HCV-specific CD4+ T cells, and in a subset of patients of HCV-specific CD8+ T cells. As the main result, we found a higher expression level of TIGIT+ PD-1+ on HCV-specific CD4+ T cells during acute and chronic HCV infection compared to patients with spontaneously resolved HCV infection (p < 0,0001). Conversely, expression of the complementary co-stimulatory receptor of TIGIT, CD226 (DNAM-1) was significantly decreased on HCV-specific CD4+ T cells during chronic infection. The predominant phenotype of HCV-specific CD4+ T cells during acute and chronic infection was TIGIT+, PD-1+, BTLA+, Tim-3-. This comprehensive phenotypic study confirms TIGIT together with PD-1 as a discriminatory marker of dysfunctional HCV-specific CD4+ T cells.
U2 - 10.1038/s41598-019-47024-8
DO - 10.1038/s41598-019-47024-8
M3 - SCORING: Journal article
C2 - 31337800
VL - 9
SP - 10624
JO - SCI REP-UK
JF - SCI REP-UK
SN - 2045-2322
IS - 1
ER -