Research into the suppressive activity of CD4＋FoxP3＋ T regulatory cells （Treg） has defined a sublineage of CD4＋ cells that contribute to self-tolerance and resistance to autoimmune disease. Much less attention ha...Research into the suppressive activity of CD4＋FoxP3＋ T regulatory cells （Treg） has defined a sublineage of CD4＋ cells that contribute to self-tolerance and resistance to autoimmune disease. Much less attention has been given to the potential contribution of regulatory sublineages of CD8＋ cells. Analysis of a small fraction of CD8＋ cells that target autoreactive CD4＋ cells through recognition of the MHC class Ib molecule Qa-1 in mouse and HLA-E in human has revitalized interest in CD8＋ Treg. Here we summarize recent progress and future directions of research into the role of this CD8＋ sublineage in resistance to autoimmune disease. Cellular ＆ Molecular Immunology. 2008; 5（6）：401-406.展开更多
AIM： To assess if a specific cytotoxic T cell response can be induced in patients with malignant liver tumors treated with radio-frequency ablation （RFA）. METHODS： Six Patients with liver metastases of colorectal ...AIM： To assess if a specific cytotoxic T cell response can be induced in patients with malignant liver tumors treated with radio-frequency ablation （RFA）. METHODS： Six Patients with liver metastases of colorectal cancer and 6 with hepatocellular carcinoma （HCC） underwent RFA. Blood was sampled before, 4 and 8 wk after RFA. Test antigens were autologous liver and tumor lysate obtained from each patient by biopsy. Peripheral T cell activation was assessed by an interferon gamma （IFNγ） secretion assay and flow cytometry. T cells were double-stained for CD4/CD8 and IFNγ to detect cytotoxic T cells. The ratio of IFNγ positive and IFNγ negative T cells was determined as the stimulation index （SI）. To assess cytolytic activity, T cells were co-incubated with human CaCo colorectal cancer and HepG2 HCC cells and release of cytosolic adenylate kinase was measured by a luciferase assay. RESULTS： Before RFA SI was 0.021 （±0.006） for CD4^＋ and 0.022 （± 0.004） for CD8^＋T cells against nonmalignant liver tissue and 0.018 （± 0.005） for CD4^＋ and 0.021 （± 0.004） for CD8^＋ cells against autologous tumor tissue. Four weeks after RFA SI against tumor tissue increased to 0.109 （± 0.005） for CD4＋ and 0.11 （± 0.012） for CD8＋ T cells against HCC, and to 0.115 （± 0.031） for CD4^＋ and 0.15 （± 0.02） for CD8^＋ cells for colorectal metastases （P 〈 0.0001）. No increased SI was observed with nonmalignant tumor tissue at all time points. Before RFA cytolytic activity against the respect（ve cancer cells was low with 2.62 （± 0.37） relative luminescence units （RLU）, but rose more than 100 fold 4 and 8 wk after RFA. Spontaneous release was 〈 2% of maximum release in all experiments. CONCLUSION： Patients with primary and secondary tumors of the liver show a significant tumor-specific cytotoxic T-cell stimulation with a dramatically increased tumor specific cytolytic activity of CD8^＋ T cells after RFA.展开更多
基金supported in part by research grants from the NIH (AI037562)National Multiple Sclerosis Society and a gift from the Schecter Family Research Foundation to HC LL is a Claudia Adams Barr Investigator and NIH NRSA Fellow (T32 AI07386)
文摘Research into the suppressive activity of CD4＋FoxP3＋ T regulatory cells （Treg） has defined a sublineage of CD4＋ cells that contribute to self-tolerance and resistance to autoimmune disease. Much less attention has been given to the potential contribution of regulatory sublineages of CD8＋ cells. Analysis of a small fraction of CD8＋ cells that target autoreactive CD4＋ cells through recognition of the MHC class Ib molecule Qa-1 in mouse and HLA-E in human has revitalized interest in CD8＋ Treg. Here we summarize recent progress and future directions of research into the role of this CD8＋ sublineage in resistance to autoimmune disease. Cellular ＆ Molecular Immunology. 2008; 5（6）：401-406.
基金Supported by the Bavarian Ministry of Economy (Leitprojekt Medizintechnik) and the Hans L(o|¨)wel Foundation, Bamberg,Germany
文摘AIM： To assess if a specific cytotoxic T cell response can be induced in patients with malignant liver tumors treated with radio-frequency ablation （RFA）. METHODS： Six Patients with liver metastases of colorectal cancer and 6 with hepatocellular carcinoma （HCC） underwent RFA. Blood was sampled before, 4 and 8 wk after RFA. Test antigens were autologous liver and tumor lysate obtained from each patient by biopsy. Peripheral T cell activation was assessed by an interferon gamma （IFNγ） secretion assay and flow cytometry. T cells were double-stained for CD4/CD8 and IFNγ to detect cytotoxic T cells. The ratio of IFNγ positive and IFNγ negative T cells was determined as the stimulation index （SI）. To assess cytolytic activity, T cells were co-incubated with human CaCo colorectal cancer and HepG2 HCC cells and release of cytosolic adenylate kinase was measured by a luciferase assay. RESULTS： Before RFA SI was 0.021 （±0.006） for CD4^＋ and 0.022 （± 0.004） for CD8^＋T cells against nonmalignant liver tissue and 0.018 （± 0.005） for CD4^＋ and 0.021 （± 0.004） for CD8^＋ cells against autologous tumor tissue. Four weeks after RFA SI against tumor tissue increased to 0.109 （± 0.005） for CD4＋ and 0.11 （± 0.012） for CD8＋ T cells against HCC, and to 0.115 （± 0.031） for CD4^＋ and 0.15 （± 0.02） for CD8^＋ cells for colorectal metastases （P 〈 0.0001）. No increased SI was observed with nonmalignant tumor tissue at all time points. Before RFA cytolytic activity against the respect（ve cancer cells was low with 2.62 （± 0.37） relative luminescence units （RLU）, but rose more than 100 fold 4 and 8 wk after RFA. Spontaneous release was 〈 2% of maximum release in all experiments. CONCLUSION： Patients with primary and secondary tumors of the liver show a significant tumor-specific cytotoxic T-cell stimulation with a dramatically increased tumor specific cytolytic activity of CD8^＋ T cells after RFA.
