OBJECTIVE: To decipher the immunologic mechanisms of plaque maturation and rupture, it is necessary to analyze the phenotypes and distribution of individual lymphocytes that migrate to the plaques, as well as their activation at different stages of plaque formation. METHODS AND RESULTS: We developed a protocol to isolate plaque-residing immune cells and analyze their status using polychromatic flow cytometry. We found that the composition and phenotype of T lymphocytes in the plaques differs from that in blood. CD4 and, in particular, CD8(+) T cells in plaques are highly activated; the fraction of CD8 T cells coexpressing CD25 and human leukocyte antigen-D related in plaques was 6 times as large as in blood. CONCLUSIONS: The first flow-cytoanalysis of individual T cells in atherosclerotic plaques indicates that plaques represent a separate immunologic compartment from blood with lymphocytes characterized by a high level of T-cell activation, which is compatible with the presence of antigen(s) that trigger infiltration activation of these cells. The ability to isolate and characterize these cells may lead to the identification of such antigens.
OBJECTIVE: To decipher the immunologic mechanisms of plaque maturation and rupture, it is necessary to analyze the phenotypes and distribution of individual lymphocytes that migrate to the plaques, as well as their activation at different stages of plaque formation. METHODS AND RESULTS: We developed a protocol to isolate plaque-residing immune cells and analyze their status using polychromatic flow cytometry. We found that the composition and phenotype of T lymphocytes in the plaques differs from that in blood. CD4 and, in particular, CD8(+) T cells in plaques are highly activated; the fraction of CD8 T cells coexpressing CD25 and human leukocyte antigen-D related in plaques was 6 times as large as in blood. CONCLUSIONS: The first flow-cytoanalysis of individual T cells in atherosclerotic plaques indicates that plaques represent a separate immunologic compartment from blood with lymphocytes characterized by a high level of T-cell activation, which is compatible with the presence of antigen(s) that trigger infiltration activation of these cells. The ability to isolate and characterize these cells may lead to the identification of such antigens.
Authors: Takahiko Naruko; Makiko Ueda; Kazuo Haze; Allard C van der Wal; Chris M van der Loos; Akira Itoh; Ryushi Komatsu; Yoshihiro Ikura; Masayuki Ogami; Yoshihisa Shimada; Shoichi Ehara; Minoru Yoshiyama; Kazuhide Takeuchi; Junichi Yoshikawa; Anton E Becker Journal: Circulation Date: 2002-12-03 Impact factor: 29.690
Authors: J S Hochman; J E Tamis; T D Thompson; W D Weaver; H D White; F Van de Werf; P Aylward; E J Topol; R M Califf Journal: N Engl J Med Date: 1999-07-22 Impact factor: 91.245
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Authors: Victor Appay; P Rod Dunbar; Margaret Callan; Paul Klenerman; Geraldine M A Gillespie; Laura Papagno; Graham S Ogg; Abigail King; Franziska Lechner; Celsa A Spina; Susan Little; Diane V Havlir; Douglas D Richman; Norbert Gruener; Gerd Pape; Anele Waters; Philippa Easterbrook; Mariolina Salio; Vincenzo Cerundolo; Andrew J McMichael; Sarah L Rowland-Jones Journal: Nat Med Date: 2002-04 Impact factor: 53.440
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Authors: Joseph C Mudd; Soumya Panigrahi; Benjamin Kyi; So Hee Moon; Maura M Manion; Souheil-Antoine Younes; Scott F Sieg; Nicholas T Funderburg; David A Zidar; Michael M Lederman; Michael L Freeman Journal: J Infect Dis Date: 2016-10-04 Impact factor: 5.226
Authors: Bonnie Chen; Stephen R Morris; Soumya Panigrahi; Gillian M Michaelson; Jonathan M Wyrick; Alexey A Komissarov; Daria Potashnikova; Anna Lebedeva; Souheil-Antoine Younes; Karem Harth; Vikram S Kashyap; Elena Vasilieva; Leonid Margolis; David A Zidar; Scott F Sieg; Carey L Shive; Nicholas T Funderburg; Sara Gianella; Michael M Lederman; Michael L Freeman Journal: J Immunol Date: 2020-03-30 Impact factor: 5.422
Authors: Anna Lebedeva; Daria Vorobyeva; Murad Vagida; Oxana Ivanova; Eugeny Felker; Wendy Fitzgerald; Natalya Danilova; Vladimir Gontarenko; Alexander Shpektor; Elena Vasilieva; Leonid Margolis Journal: Atherosclerosis Date: 2017-10-07 Impact factor: 5.162
Authors: Scott F Sieg; Douglas A Bazdar; David Zidar; Michael Freeman; Michael M Lederman; Nicholas T Funderburg Journal: Immunology Date: 2019-11-21 Impact factor: 7.397