title: CLTA-4 blockade in vivo promotes the generation of short-lived effector CD8 T cells and a more persistent central memory CD4 T cell response.
abstract: BACKGROUND
  Previously, we examined the effects of in vivo CTLA-4 blockade using a fully human monoclonal antibody as a part of a DNA vaccination regimen in cynomolgus macaques (Macaca fascicularis). We observed that while the antibody had little effect on the IFN-gamma ELISpot response, CTLA-4 blockade enhanced antigen-specific cellular proliferation in both CD4(+) and CD8(+)T-cell compartments.
  
  
  METHODS
  We examine the specific effects of CTLA-4 blockade on memory T-cell compartments following the third immunization and 10 months following a fourth immunization, during the memory phase of the immune response.
  
  
  RESULTS
  CLTA-4 blockade enhanced CD4(+) and CD8(+) central memory (CD28(hi), CD95(hi)) T-cell responses as well as a short-lived CD8(+) effector (CD28(lo), CD95(hi)) T-cell response.
  
  
  CONCLUSIONS
  These data suggest differing effects of CTLA-4 blockade on CD4(+) and CD8(+) T cells with implications on the clinical use of anti-CTLA-4 antibodies for enhancement of vaccine strategies or treatment of human disease.
authors.affiliation: Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Hokey
authors.forename: Jian
authors.initials: J
authors.lastname: Yan
authors.forename: Lauren A
authors.initials: LA
authors.lastname: Hirao
authors.forename: Anlan
authors.initials: A
authors.lastname: Dai
authors.forename: Jean D
authors.initials: JD
authors.lastname: Boyer
authors.forename: Maria N
authors.initials: MN
authors.lastname: Jure-Kunkel
authors.forename: David B
authors.initials: DB
authors.lastname: Weiner
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000276:immunology* / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D060908:CTLA-4 Antigen; D005260:Female; D005434:Flow Cytometry; D007156:Immunologic Memory / Q000276:immunology*; D008252:Macaca fascicularis; D008297:Male; D018448:Models, Immunological; D019444:Vaccines, DNA / Q000008:administration & dosage
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D019444:Vaccines, DNA