title: Reduced efficacy of circulating costimulatory cells after focal cerebral ischemia.
abstract: OBJECTIVE
  Cerebral ischemia is ensued by a cellular immune depression syndrome. The postischemic functional capacity of T lymphocytes is controversial, and interactions between leukocyte subsets are largely unknown. Understanding the immunologic interplay between antigen-presenting cells and lymphocytes as well as between distinct lymphocyte subsets after stroke might be of clinical/therapeutic significance because animal data argue for a cerebroprotective effect of, for example, CD4+CD25+ regulatory T cells.
  
  
  METHODS
  Ex vivo CD4+ T cell proliferation was analyzed in experimental and human stroke using fluorescence activated cell sorter analysis. To investigate suppressive effects of CD4+CD25+ regulatory T cells as well as the influence of costimulatory cells on CD4+ T cell proliferation, subsets were magnetically sorted before proliferation assay setup.
  
  
  RESULTS
  After stroke: (1) proliferation of mouse and human CD4+ T cells on T cell receptor stimulation was unaltered; (2) the suppressive effect of CD4+CD25+ regulatory T cells in mouse and man was unaltered; and (3) efficacy of circulating costimulatory cells from stroke animals was reduced by a mean of 0.6 (SEM 0.1, P=0.001) CD4+ T cell division numbers compared with sham-treated animals.
  
  
  CONCLUSIONS
  Reduced costimulatory efficacy of circulating costimulatory cells in mice is an important feature of stroke-induced immunodepression. Understanding the interplay of costimulatory cells and responder T cells (eg, CD4+ T cells or CD4+CD25+ regulatory T cells) after stroke may offer new insights into the prevention of secondary inflammatory damage to the brain and help to guide new therapeutic strategies.
authors.affiliation: Spinal Cord Injury Center, Department of Neurology, Neuroradiology, and Hygiene and Medical Microbiology, University Hospital of Heidelberg, Schlierbacher Landstr. 200a, 69118 Heidelberg, Germany. andreas.hug@med.uni-heidelberg.de
authors.forename: Andreas
authors.initials: A
authors.lastname: Hug
authors.forename: Arthur
authors.initials: A
authors.lastname: Liesz
authors.forename: Bettina
authors.initials: B
authors.lastname: Muerle
authors.forename: Wei
authors.initials: W
authors.lastname: Zhou
authors.forename: Julia
authors.initials: J
authors.lastname: Ehrenheim
authors.forename: Alexander
authors.initials: A
authors.lastname: Lorenz
authors.forename: Alexander
authors.initials: A
authors.lastname: Dalpke
authors.forename: Roland
authors.initials: R
authors.lastname: Veltkamp
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D051379:Mice; D020521:Stroke / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology