Frequency of gC1qR+CD4+ T cells increases during acute hepatitis C virus infection and remains elevated in patients with chronic infection.
CD4+ T cell responses are impaired in chronic HCV infection. To determine factor(s) involved in CD4+ T cell dysregulation, we examined the effect of extracellular core on the alteration of CD4+ T cell responses and the cell surface level of core-binding protein, gC1qR on CD4+ T cells from acute HCV patients with resolved and chronic infection. During the acute phase of infection, the frequency of gC1qR+CD4+ T cells increased in both resolved and chronic HCV infection compared to healthy controls. Notably, 6 months later, the frequency of gC1qR+CD4+ T cells maintained elevated in chronic patients compared to that in resolved patients. In addition, TCR stimulation increased the frequency of gC1qR+CD4+ T cells, resulting in core-induced inhibition of T cell responses in both resolved and chronic patients. These results suggest that HCV infection expands gC1qR+CD4+ T cells, which increase the susceptibility to core-mediated immune dysregulation and facilitate the establishment of HCV persistency.
Cummings
Kara L
KL
Beirne Carter Center for Immunology Research and Department of Microbiology, University of Virginia, Charlottesville, VA 22908, USA.
Rosen
Hugo R
HR
Hahn
Young S
YS
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D006526:Hepatitis C / Q000097:blood / Q000276:immunology*; D018936:Hepatitis C Antigens / Q000097:blood / Q000276:immunology / Q000494:pharmacology; D019698:Hepatitis C, Chronic / Q000097:blood / Q000276:immunology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008297:Male; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D014758:Viral Core Proteins / Q000097:blood / Q000276:immunology / Q000494:pharmacology; D055815:Young Adult
C087299:C1QBP protein, human; D002352:Carrier Proteins; D018936:Hepatitis C Antigens; D024101:Mitochondrial Proteins; D011948:Receptors, Antigen, T-Cell; D014758:Viral Core Proteins; C499352:core protein p22, Hepatitis C virus