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Sci Rep. 2019 Jul 23;9(1):10624. doi: 10.1038/s41598-019-47024-8.

HCV-specific CD4+ T cells of patients with acute and chronic HCV infection display high expression of TIGIT and other co-inhibitory molecules.

Author information

1
I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
2
Department of Medicine II, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
3
Faculty of Biology, University of Freiburg, Freiburg, Germany.
4
DZIF partner site (German Center for Infection Research), Hamburg, Germany.
5
Department of Transfusion Medicine, Germany, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
6
Gastroenterologie und Hepatologie; Kantonsspital Aarau, Aarau, Switzerland.
7
Benaroya Research Institute at Virginia Mason, Seattle, Washington, United States of America.
8
Protozoa Immunology, Bernhard Nocht, Institute for Tropical Medicine, Hamburg, Germany.
9
I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. julianszw@gmail.com.
10
DZIF partner site (German Center for Infection Research), Hamburg, Germany. julianszw@gmail.com.

Abstract

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.

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