title: Atopic asthma: differential activation phenotypes among memory T helper cells.
abstract: BACKGROUND
  T cells have been implicated in the pathogenesis of atopic asthma. We have previously shown that memory T helper cells (CD4+CD45RO+) are preferentially activated relative to naïve T helper cells (CD4+CD45RA+) after bronchial allergen challenge. However, specific T helper subpopulations that are activated in atopy and/or asthma remain undefined.
  
  
  OBJECTIVE
  To determine the T helper subpopulations and activation phenotypes relevant to acute and stable asthma that may be common with or distinct from atopy.
  
  
  METHODS
  Two groups of atopic asthmatics (ten acute and nine stable asthmatics) and two non-asthmatic groups (14 non-asthmatic atopics and eight normal non-atopic controls) were analysed. Ten acute asthmatics were assessed in the emergency room during an acute episode (FEV1 43.6% +/- 18.4). Nine stable asthmatics were assessed during a symptom-free period (FEV1 85% +/- 6). Using multiple colour flow cytometry we analysed T cell subpopulations and the expression of IL-2-receptor (IL-2R) and MHC-class II antigens (MHC II) on naïve and memory T helper cells in the peripheral blood of asthmatic and non-asthmatic groups.
  
  
  RESULTS
  Atopic asthmatics (acute and stable) had an increased percentage of memory T helper cells expressing IL-2R compared with normal non-atopics (mean SD 16.1 +/- 6%, 12.4 +/- 2% and 7.7 +/- 1.8%, P < 0.05) but not compared with non-asthmatic atopics (10 +/- 3.5%). Naïve T helper cells had low expression of IL-2R and MHC II in all four groups. MHC II antigen expression was increased in memory T helper cells of asthmatics (acute and stable) compared with normal non-atopics (13.9 +/- 7.5, 10.6 +/- 5 and 4.9 +/- 2.5, P < 0.05) but not compared with non-asthmatic atopics (7.92 4). A novel finding was that IL-2R and the MHC II molecules were mainly expressed in non-overlapping populations and coexpression was found predominantly on memory T helper cells. Asthmatics (acute and stable) had higher proportion of double positive memory T helper cells (IL-2R+MHC II+) compared with both non-asthmatic groups (P < 0.05).
  
  
  CONCLUSIONS
  We demonstrate a differential expression of IL-2R+ and MCH II+ on CD45RO+ T helper cells that would suggest that there are three subsets of activated memory T helper cells in asthmatics. Two non-overlapping IL-2R+ or MHC II+ CD45RO+ T helper cells and a third subpopulation of activated cells that coexpress IL-2R and MHC II (double positives). This latter subpopulation is significantly higher in asthmatics (acute or stable) compared with both non-asthmatic groups, suggesting a specific T helper activation phenotype distinct to atopic asthmatics as compared with atopic non-asthmatics.
authors.affiliation: Respiratory Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: M L
authors.initials: ML
authors.lastname: Lara-Marquez
authors.forename: M J
authors.initials: MJ
authors.lastname: Moan
authors.forename: S
authors.initials: S
authors.lastname: Cartwright
authors.forename: J
authors.initials: J
authors.lastname: Listman
authors.forename: E
authors.initials: E
authors.lastname: Israel
authors.forename: D L
authors.initials: DL
authors.lastname: Perkins
authors.forename: D C
authors.initials: DC
authors.lastname: Christiani
authors.forename: P W
authors.initials: PW
authors.lastname: Finn
mesh_terms: D000208:Acute Disease; D000328:Adult; D001249:Asthma / Q000276:immunology* / Q000503:physiopathology; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry / Q000276:immunology; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000276:immunology*; D007156:Immunologic Memory / Q000276:immunology*; D016130:Immunophenotyping / Q000379:methods*; D017493:Leukocyte Common Antigens / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000737:chemistry / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000737:chemistry / Q000276:immunology*
chemical_list: D000949:Histocompatibility Antigens Class II; D015375:Receptors, Interleukin-2; D017493:Leukocyte Common Antigens