Research Interests: Immunology, Biology, Macrophages, Immunology of the Gut, Medicine, and 15 moreToll Like Receptors, Cell line, Mice, Animals, DNA methylation, NF-kappa B, T lymphocytes, B Lymphocytes, NF κB, Protein Binding, Ligands, Gene Expression Regulation, binding sites, conserved sequence , and Programmed Cell Death 1 Receptor
Viral infections induce extensive T cell proliferation in vivo. However, only a small fraction (1-5%) of the activated T cells have been shown to be virus specific leading to the prevailing notion that most of the T cell expansion... more
Viral infections induce extensive T cell proliferation in vivo. However, only a small fraction (1-5%) of the activated T cells have been shown to be virus specific leading to the prevailing notion that most of the T cell expansion represents cytokine-mediated by-stander activation and/or cross reactive stimulation of non specific cells. To re-examine this issue we quantitated antigen specific CD8 T cells during acute LCMV infection of mice using three sensitive techniques: (i) intracellular cytokine production, (ii) single cell ELISPOT and (iii) direct visualization of antigen specific CD8 T cells by staining with MHC class I tetramers + peptide. In contrast to previous estimates, we found that 50-70% of the activated CD8 T cells were LCMV specific. This represented > or = 10,000-fold increase (approximately 2 x 10(7) virus specific cells/spleen) in 8 days with the peak expansion occurring between day 3 and 5 during which period virus specific CD8 T cells had an estimated division time of approximately 8 hours. Following viral clearance, the number of antigen specific CD8 T cells dropped to 1 x 10(6) per spleen and were maintained at this level for the life of the mouse. Upon rechallenge with LCMV, memory CD8 T cells rapidly proliferated and again comprised > 50% of the total CD8 T cells. In contrast, upon challenge with a heterologous virus such as vaccinia, there was no change in the number of LCMV specific memory CTL, despite a substantial increase in the number of activated CD8 T cells. Taken together, these results show that much of the CD8 T cell expansion seen during viral infection represents antigen specific cells.
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Memory is a hallmark of the immune system and ever since its recognition there has been considerable interest in understanding how immunity is maintained. The current model is that long-term memory is dependent on persistent antigenic... more
Memory is a hallmark of the immune system and ever since its recognition there has been considerable interest in understanding how immunity is maintained. The current model is that long-term memory is dependent on persistent antigenic stimulation. We report here results that challenge this view and provide evidence that antigen is not essential for the maintenance of CD8+ T-cell memory. We show that memory CD8+ cytotoxic T lymphocytes persist indefinitely in the absence of priming antigen, retain the memory phenotype (CD44hi), and provide protection against virus challenge. These findings suggest a re-evaluation of our current thinking on mechanisms involved in maintaining immunity and have implications towards designing effective vaccination strategies.
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Recombinant vaccinia viruses (rVV) have been extensively used as vaccines, but there is little information about the total magnitude of the VV-specific T-cell response and how this compares to the immune response to the foreign gene(s)... more
Recombinant vaccinia viruses (rVV) have been extensively used as vaccines, but there is little information about the total magnitude of the VV-specific T-cell response and how this compares to the immune response to the foreign gene(s) expressed by the rVV. To address this issue, we quantitated the T-cell responses to both the viral vector and the insert following the infection of mice with VV expressing a cytotoxic T lymphocyte (CTL) epitope (NP118-126) from lymphocytic choriomeningitis virus (LCMV). The LCMV epitope-specific response was quantitated by intracellular cytokine staining after stimulation with the specific peptide. To analyze the total VV-specific response, we developed a simple intracellular cytokine staining assay using VV-infected major histocompatibility complex class I and II matched cells as stimulators. Using this approach, we made the following determinations. (i) VV-NP118 induced potent and long-lasting CD8 and CD4 T-cell responses to the vector; at the peak ...
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... Nobuhiro Nakamoto, David E. Kaplan, Jennifer Coleclough, Yun Li, Mary E. Valiga, MaryKaminski, Abraham Shaked, Kim Olthoff, Emma Gostick, David A. Price, Gordon J. Freeman, E. John Wherry, KyongMi Chang Gastroenterology June 2008... more
... Nobuhiro Nakamoto, David E. Kaplan, Jennifer Coleclough, Yun Li, Mary E. Valiga, MaryKaminski, Abraham Shaked, Kim Olthoff, Emma Gostick, David A. Price, Gordon J. Freeman, E. John Wherry, KyongMi Chang Gastroenterology June 2008 (Vol. ...
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Research Interests: Engineering, Microbiology, Biology, Medicine, Iran, and 15 moreBiological Sciences, Humans, Child, Salmonella enteritidis, Polymerase Chain Reaction, Infant, Phenotype, Salmonella, Microbial Sensitivity Tests, Amino Acid Substitution Rates, Beta Lactamases, Molecular Sequence Data, Child preschool, Foodborne, and Medical and Health Sciences
T-cell tolerance to self antigens is maintained by events that occur within the thymus and in the periphery. Mechanisms that operate on immature T cells within the thymus are effective in induction of tolerance to viruses, but mechanisms... more
T-cell tolerance to self antigens is maintained by events that occur within the thymus and in the periphery. Mechanisms that operate on immature T cells within the thymus are effective in induction of tolerance to viruses, but mechanisms of tolerizing mature T cells are likely to break down. This failure of peripheral mechanisms to induce T-cell tolerance to viruses has implications for autoimmunity and for treatment of chronic viral infections.