Comparing CD4+ T cells generated during acute or chronic hepatitis C virus (HCV) infection, Reinscheid and Weisser et al. evaluated patient samples and found that acute infection generated various subsets of progenitor CD4+ T cells, including subsets also observed in chronic infection. In chronic infection, a subset of stem-like/resting Bcl-2+ CD4+ T cells likely gave rise to a subset of T-bet+ effector CD4+ T cells. In patients treated with DAA to clear the virus, the effector subset essentially disappeared, while the stem-like subset formed a functional long-term memory pool that was distinct from the memory pools that formed after spontaneous HCV clearance.
Contributed by Lauren Hitchings
ABSTRACT: Virus-specific CD4(+) T cells are essential for coordinating adaptive immunity during infection, but their differentiation and maintenance in chronic infection remain unclear. Using human hepatitis C virus (HCV) infection as a model, we assessed the determinants of virus-specific CD4(+) T cell immunity in acute, spontaneously cleared, chronic, and therapeutically cured infections. During acute infection, multiple subsets of progenitor CD4(+) T cells emerged, including subsets that are also found in chronic infection. In chronic infection, stem-like Bcl-2(+) CD4(+) T cells and T-bet(+) effector CD4(+) T cells existed in a progenitor/progeny relationship. Following therapy-mediated HCV cure, these cells retained their chronic signature but formed a stable memory pool that persisted for years and was distinct from HCV-specific CD4(+) T cell memory after spontaneous clearance. Collectively, our findings highlight differences in CD4(+) T cell fates that depend on infection outcomes and reveal common principles of CD4(+) and exhausted CD8(+) T cell maintenance during and after chronic infection.
Author Info: (1) Department of Medicine II, Medical Center - University of Freiburg, Hugstetter Str. 55, D-79106 Freiburg, Germany; Faculty of Biology, University of Freiburg, Freiburg, Germany
Author Info: (1) Department of Medicine II, Medical Center - University of Freiburg, Hugstetter Str. 55, D-79106 Freiburg, Germany; Faculty of Biology, University of Freiburg, Freiburg, Germany. (2) Department of Medicine II, Medical Center - University of Freiburg, Hugstetter Str. 55, D-79106 Freiburg, Germany; Faculty of Biology, University of Freiburg, Freiburg, Germany. (3) Department of Medicine II, Medical Center - University of Freiburg, Hugstetter Str. 55, D-79106 Freiburg, Germany; Faculty of Medicine, University of Freiburg, Freiburg, Germany. (4) Department of Medicine II, Medical Center - University of Freiburg, Hugstetter Str. 55, D-79106 Freiburg, Germany; Faculty of Medicine, University of Freiburg, Freiburg, Germany. (5) Department of Medicine II, Medical Center - University of Freiburg, Hugstetter Str. 55, D-79106 Freiburg, Germany; Faculty of Medicine, University of Freiburg, Freiburg, Germany. (6) Department of Medicine II, Medical Center - University of Freiburg, Hugstetter Str. 55, D-79106 Freiburg, Germany; Faculty of Biology, University of Freiburg, Freiburg, Germany. (7) Department of Medicine II, Medical Center - University of Freiburg, Hugstetter Str. 55, D-79106 Freiburg, Germany; Faculty of Medicine, University of Freiburg, Freiburg, Germany. (8) Department of Medicine II, Medical Center - University of Freiburg, Hugstetter Str. 55, D-79106 Freiburg, Germany; Faculty of Biology, University of Freiburg, Freiburg, Germany. (9) Institute for Transfusion Medicine and Gene Therapy, Freiburg University Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany. (10) Institute of Virology, Medical Faculty and University Hospital Dsseldorf, Heinrich Heine University Dsseldorf, Dsseldorf, Germany. (11) Institute of Virology, Medical Faculty and University Hospital Dsseldorf, Heinrich Heine University Dsseldorf, Dsseldorf, Germany. (12) Department of Medicine II, Medical Center - University of Freiburg, Hugstetter Str. 55, D-79106 Freiburg, Germany; Faculty of Biology, University of Freiburg, Freiburg, Germany. (13) Institute of Virology, Medical Faculty and University Hospital Dsseldorf, Heinrich Heine University Dsseldorf, Dsseldorf, Germany. (14) Institute of Molecular and Clinical Ophthalmology Basel, Basel, Switzerland. (15) Department of Medicine II, Medical Center - University of Freiburg, Hugstetter Str. 55, D-79106 Freiburg, Germany; Faculty of Medicine, University of Freiburg, Freiburg, Germany; German Cancer Consortium (DKTK), Heidelberg, Germany, partner site Freiburg, Freiburg, Germany; Signaling Research Centers BIOSS and CIBSS, Freiburg, Germany. (16) Department of Medicine II, Medical Center - University of Freiburg, Hugstetter Str. 55, D-79106 Freiburg, Germany; Faculty of Medicine, University of Freiburg, Freiburg, Germany. (17) Department of Medicine II, Medical Center - University of Freiburg, Hugstetter Str. 55, D-79106 Freiburg, Germany; Faculty of Medicine, University of Freiburg, Freiburg, Germany. Electronic address: robert.thimme@uniklinik-freiburg.de. (18) Department of Medicine II, Medical Center - University of Freiburg, Hugstetter Str. 55, D-79106 Freiburg, Germany; Faculty of Medicine, University of Freiburg, Freiburg, Germany. Electronic address: tobias.boettler@uniklinik-freiburg.de. (19) Department of Medicine II, Medical Center - University of Freiburg, Hugstetter Str. 55, D-79106 Freiburg, Germany; Faculty of Medicine, University of Freiburg, Freiburg, Germany. Electronic address: maike.hofmann@uniklinik-freiburg.de.
