tetano
Editor, Senior Moderator
European Journal of Immunology
Avidity of influenza-specific memory CD8+ T-cell populations decays over time compromising antiviral immunity
Ian R. Humphreys1,*,
Mathew Clement1,
Morgan Marsden1,
Kristin Ladell1,
James E. McLaren1,
Kathryn Smart1,
James P. Hindley1,
Hayley M. Bridgeman1,
Hugo A. van den Berg2,
David A. Price1,
Ann Ager1,
Linda Wooldridge1,
Andrew Godkin1,
Awen M. Gallimore1,*
DOI: 10.1002/eji.201242575
Decline of cell-mediated immunity is often attributed to decaying T-cell numbers and their distribution in peripheral organs. This study examined the hypothesis that qualitative as well as quantitative changes contribute to the declining efficacy of CD8+ T-cell memory. Using a model of influenza virus infection, where loss of protective CD8+ T-cell immunity was observed 6 months post-infection, we found no decline in antigen-specific T-cell numbers or migration to the site of secondary infection. There was, however, a large reduction in antigen-specific CD8+ T-cell degranulation, cytokine secretion and polyfunctionality. A profound loss of high avidity T cells over time indicated that failure to confer protective immunity resulted from the inferior functional capacity of remaining low avidity cells. These data imply that high avidity central memory T cells wane with declining antigen levels, leaving lower avidity T cells with reduced functional capabilities.
http://scienceindex.com/stories/250...romising_antiviral_immunity.html#.UFFxe1Lwo0U
Avidity of influenza-specific memory CD8+ T-cell populations decays over time compromising antiviral immunity
Ian R. Humphreys1,*,
Mathew Clement1,
Morgan Marsden1,
Kristin Ladell1,
James E. McLaren1,
Kathryn Smart1,
James P. Hindley1,
Hayley M. Bridgeman1,
Hugo A. van den Berg2,
David A. Price1,
Ann Ager1,
Linda Wooldridge1,
Andrew Godkin1,
Awen M. Gallimore1,*
DOI: 10.1002/eji.201242575
Decline of cell-mediated immunity is often attributed to decaying T-cell numbers and their distribution in peripheral organs. This study examined the hypothesis that qualitative as well as quantitative changes contribute to the declining efficacy of CD8+ T-cell memory. Using a model of influenza virus infection, where loss of protective CD8+ T-cell immunity was observed 6 months post-infection, we found no decline in antigen-specific T-cell numbers or migration to the site of secondary infection. There was, however, a large reduction in antigen-specific CD8+ T-cell degranulation, cytokine secretion and polyfunctionality. A profound loss of high avidity T cells over time indicated that failure to confer protective immunity resulted from the inferior functional capacity of remaining low avidity cells. These data imply that high avidity central memory T cells wane with declining antigen levels, leaving lower avidity T cells with reduced functional capabilities.
http://scienceindex.com/stories/250...romising_antiviral_immunity.html#.UFFxe1Lwo0U