title: CD101 expression and function in normal and rheumatoid arthritis-affected human T cells and monocytes/macrophages.
abstract: OBJECTIVE
  It was recently reported that CD101 surface expression discriminates potency among CD4+CD25+ FoxP3+ regulatory T cells in the mouse. We investigated whether CD101 may also have a role in the suppressor function of regulatory T cells in humans given that the latter population may affect the autoimmune response in patients with rheumatoid arthritis (RA).
  
  
  METHODS
  Sorted T cells and monocyte/macrophage cell populations were analyzed by flow cyto metry using conjugated antibodies specific for cell-surface markers. T cell proliferation assays were conducted by [(3)H]thymidine incorporation and CD8(high) cytotoxicity measurements by Cyto-Scan-LDH cytotoxicity assays. ELISA were used to measure cytokines in cell culture supernatants and Western blotting was performed for profiling mitogen-activated protein (MAP) kinase activation using specific antiphospholipid antibodies.
  
  
  RESULTS
  CD101 expression coincided with PMA-induced monocyte/leukocyte lineage differentiation. CD8(high)CD101- T cells exhibited greater cytotoxic activity than CD8(high)CD101+ T cells, while no difference was observed between CD4CD25(high)CD101+ and CD4CD25(high)CD101- Treg inhibitory activity through responder T cells. LPS-induced proinflammatory cytokine production and p38 MAP kinase activation were made possible by ligation of CD101 with an anti-CD101 antibody F(ab')(2) fragment.
  
  
  CONCLUSIONS
  These results suggested a modulatory/coregulatory function of CD101 in the human immune system, in contrast to murine models, in which CD101 surface expression discriminates potency among FoxP3+ regulatory T cells. Cytotoxic CD8(high)CD101+ T cells were markedly less cytotoxic than CD8(high) T cells negative for the CD101 antigen and were conspicuously downregulated in patients with RA, suggesting a possible role for CD101 expression and function in the control of certain manifestations of RA pathology.
authors.affiliation: Division of Rheumatology and Clinical Immunology, Royal Victoria Hospital, Montreal, Quebec H3A 1A1, Canada.
authors.forename: Dragan V
authors.initials: DV
authors.lastname: Jovanovic
authors.forename: Laurence
authors.initials: L
authors.lastname: Boumsell
authors.forename: Armand
authors.initials: A
authors.lastname: Bensussan
authors.forename: Xavier
authors.initials: X
authors.lastname: Chevalier
authors.forename: Arturo
authors.initials: A
authors.lastname: Mancini
authors.forename: John A
authors.initials: JA
authors.lastname: Di Battista
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000276:immunology*; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D002460:Cell Line; D049109:Cell Proliferation; D016207:Cytokines / Q000276:immunology; D006801:Humans; D008264:Macrophages / Q000166:cytology / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D009000:Monocytes / Q000166:cytology / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D015703:Antigens, CD; C093213:CD101 antigen, human; D016207:Cytokines; D008562:Membrane Glycoproteins; D048051:p38 Mitogen-Activated Protein Kinases