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Containment of hepatitis C virus (HCV) and other chronic human viral infections is associated with persistence of virus-specific CD4 T cells, but ex vivo characterization of circulating CD4 T cells has not been achieved. To further define the phenotype and function of these cells, we developed a novel approach for the generation of tetrameric forms of MHC(More)
Hepatitis C virus (HCV) becomes persistent in the majority of infected individuals. In doing so, the virus evades host adaptive immune responses, although the mechanisms responsible in this evasion are not clear. Several groups have demonstrated weak or absent HCV-specific CD4+ T cell responses during chronic HCV infection using proliferation assays and,(More)
We compared T-cell proliferative responses to acetylcholine receptor (AChR) and to purified protein derivative (PPD) (of tuberculin) of hyperplastic thymus, thymoma, and blood cells from patients with myasthenia gravis (MG). Hyperplastic MG thymus cells gave significantly higher and more consistent responses to AChR than parallel cultures of autologous(More)
Hepatitis C virus (HCV) infection is very common worldwide, but has a broad range of outcomes. A minority of patients are able to clear infection spontaneously, and this is thought to be due to the emergence and maintenance of effective cell-mediated immunity, particularly CD4+ T lymphocyte responses. Furthermore, genetic studies have indicated that HLA(More)
Effective long-term antiviral immunity requires specific cytotoxic T lymphocytes and CD4(+) T lymphocyte help. Failure of these helper responses can be a principle cause of viral persistence. We sought evidence that variation in HIV-1 CD4(+) T helper epitopes might contribute to this phenomenon. To determine this, we assayed fresh peripheral blood(More)
Hepatitis C virus (HCV) readily sets up a persistent infection and is a major cause of liver disease worldwide. Interferon alfa and ribavirin therapy lead to sustained clearance of virus in 31% to 64% of patients with type 1 and non-type 1 genotypes, respectively. It is not clear to what extent these drugs act directly to reduce HCV replication, or(More)
Mutations in human immunodeficiency virus (HIV) cluster in cytotoxic T lymphocyte (CTL) epitopes (Phillips, R. E. et al., Nature 1991. 354: 453) and are subject to immune-mediated positive selection (Price, D. A. et al., Proc. Natl. Acad. Sci. USA 1997. 94: 1890). We studied the effects of naturally occurring mutations in the HIV-1 p17 Gag HLA A2 restricted(More)
Hepatitis C virus (HCV) has infected over 170 million people world wide, and in the majority sets up a chronic infection associated with hepatic inflammation. How it evades host immunity, particularly CD8+ T cells (CTL) is unclear, but two major factors are likely to operate, viral escape mutation and T cell exhaustion. We have investigated the role of CTL(More)
Natural killer T (NKT) cells are thought to be involved in innate responses against infection. We investigated one specific type of NKT cell, Valpha24/Vbeta11 double positive, in hepatitis C virus (HCV) infection. Lower frequencies of this population were detected in the blood of HCV PCR-positive patients than in controls. Unlike Valpha24/Vbeta11 NKT cells(More)
Peripheral blood lymphocytes from 23 of 114 (20%) myasthenia gravis (MG) patients showed positive T-cell proliferative responses to native acetylcholine receptor (AChR) purified from the electric fish Torpedo, compared with two of 25 (8%) healthy or other neurologic disease controls. Responsiveness appeared to fluctuate seasonally. Long-term T-cell lines(More)