title: Human CD4+CD25+ T cells derived from the majority of atopic donors are able to suppress TH1 and TH2 cytokine production.
abstract: BACKGROUND
  Recently, it has been established that CD4(+)CD25(+) T cells with regulatory capacity are present in human peripheral blood, inhibiting allogeneic proliferation and cytokine production of preactivated CD4(+)CD25(-) respond-er T cells.
  
  
  OBJECTIVE
  The aim of this study was to analyze in an allergen-specific setting whether such regulatory CD4(+)CD25(+) T cells also exist and function normally in atopic individuals, especially concerning the inhibition of T(H)2 cytokines.
  
  
  METHODS
  For this purpose, CD4(+)CD25(-) or CD4(+)CD25(+) T cells from donors allergic to grass or birch pollen (mainly with rhinitis) or from healthy nonatopic donors were stimulated in the presence of autologous, mature, monocyte-derived, allergen-pulsed dendritic cells, and the preactivated CD4(+)CD25(+) T cells were added to CD4(+)CD25(-) T cells during restimulation.
  
  
  RESULTS
  CD4(+)CD25(+) T cells from the nonatopic donors and from the majority of the patients investigated proliferated poorly, produced fewer cytokines, and inhibited the proliferation and T(H)1 (IFN-gamma) and T(H)2 (IL-4 and IL-5) cytokine production of CD4(+)CD25(-) T cells but not IL-10 production. The suppression of CD4(+)CD25(-) T cells by CD4(+)CD25(+) T cells was at least partially antigen unspecific and not reversible with anti-IL-10, anti-transforming growth factor beta, or anti-cytotoxic T lymphocyte-associated antigen 4 mAb but was reversible with IL-2. In some atopic patients preactivated CD4(+)CD25(+) T cells reproducibly showed strong proliferative responses, produced higher amounts of IL-4 and IL-10 than CD4(+)CD25(-) T cells, and suppressed only the IFN-gamma production of CD4(+)CD25(-) T cells.
  
  
  CONCLUSIONS
  These data indicate that regulatory CD4(+)CD25(+) T cells are present and functional in most atopic patients with allergic rhinitis and are able to inhibit T(H)1, as well as T(H)2, cytokine production.
authors.affiliation: Department of Dermatology, University of Mainz, Mainz.
authors.forename: Iris
authors.initials: I
authors.lastname: Bellinghausen
authors.forename: Bettina
authors.initials: B
authors.lastname: Klostermann
authors.forename: Jürgen
authors.initials: J
authors.lastname: Knop
authors.forename: Joachim
authors.initials: J
authors.lastname: Saloga
mesh_terms: D000069594:Abatacept; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000502:physiology; D015704:CD4 Antigens / Q000032:analysis*; D060908:CTLA-4 Antigen; D016207:Cytokines / Q000096:biosynthesis*; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology*; D018796:Immunoconjugates; D016130:Immunophenotyping; D016753:Interleukin-10 / Q000502:physiology; D008213:Lymphocyte Activation; D015375:Receptors, Interleukin-2 / Q000032:analysis*; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000502:physiology
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; D015704:CD4 Antigens; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D016207:Cytokines; D018796:Immunoconjugates; D015375:Receptors, Interleukin-2; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D000069594:Abatacept