title: Two distinct functional patterns of hepatitis C Virus (HCV)-specific T cell responses in seronegative, aviremic patients.
abstract: In hepatitis C Virus (HCV) high-risk groups, HCV-specific T cell responses have been detected in seronegative, aviremic persons who have no evidence of HCV infection. Herein, we investigated functional profiles of HCV-specific T-cell responses in seronegative, aviremic patients of a HCV high-risk group. Seventy seven hemodialysis patients with chronic renal disease were analyzed by IFN-γ ELISpot assays, and eight of 71 (11.3%) seronegative, aviremic patients displayed HCV-specific T-cell responses. Their HCV-specific memory T cells were characterized by assessing cytokine polyfunctionality, known to provide antiviral protection. By intracellular staining of IFN-γ, TNF-α, IL-2 and MIP-1β, we identified two distinct populations in the seronegative, aviremic patients: polyfunctional responders and TNF-α-predominant responders. In further analysis, occult HCV infection was excluded as a cause of the HCV-specific T cell response via secondary nested RT-PCR of HCV RNA in peripheral blood mononuclear cell samples. HCV-specific T cells targeted multiple epitopes including non-structural proteins in a single patient, implying that their T cells might have been primed by HCV proteins synthesized within the host. We conclude that HCV-specific memory T cells of seronegative, aviremic patients arise from authentic HCV replication in the host, but not from current occult HCV infection. By functional pattern of HCV-specific T cells, there are two distinct populations in these patients: polyfunctional responders and TNF-α-predominant responders.
authors: Laboratory of Immunology and Infectious Diseases, Graduate School of Medical Science and Engineering, KAIST, Daejeon, Republic of Korea.
authors: Yoon Seok
authors: YS
authors: Choi
authors: Jung Eun
authors: JE
authors: Lee
authors: Seung Joo
authors: SJ
authors: Nam
authors: Jung Tak
authors: JT
authors: Park
authors: Hyon-Suk
authors: HS
authors: Kim
authors: Kyu Hun
authors: KH
authors: Choi
authors: Beom Seok
authors: BS
authors: Kim
authors: Eui-Cheol
authors: EC
authors: Shin
mesh_terms: D000368:Aged; D016207:Cytokines / Q000032:analysis / Q000276:immunology; D005260:Female; D018023:HIV Seronegativity; D016174:Hepacivirus / Q000276:immunology*; D006526:Hepatitis C / Q000097:blood / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis; D013601:T-Lymphocytes / Q000276:immunology* / Q000821:virology
chemical_list: D016207:Cytokines
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