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Demonstration of circulating allergen-specific CD4+CD25highFoxp3+ T-regulatory cells in both nonatopic and atopic individuals  Laura Maggi, BSc, Veronica.

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Presentation on theme: "Demonstration of circulating allergen-specific CD4+CD25highFoxp3+ T-regulatory cells in both nonatopic and atopic individuals  Laura Maggi, BSc, Veronica."— Presentation transcript:

1 Demonstration of circulating allergen-specific CD4+CD25highFoxp3+ T-regulatory cells in both nonatopic and atopic individuals  Laura Maggi, BSc, Veronica Santarlasci, MD, Francesco Liotta, MD, Francesca Frosali, BSc, Roberta Angeli, BSc, Lorenzo Cosmi, MD, Enrico Maggi, MD, Sergio Romagnani, MD, Francesco Annunziato, PhD  Journal of Allergy and Clinical Immunology  Volume 120, Issue 2, Pages (August 2007) DOI: /j.jaci Copyright © 2007 American Academy of Allergy, Asthma & Immunology Terms and Conditions

2 Fig 1 Experimental protocol used to assess antigen-specific Treg cells. Flow-cytometric evaluation of CD14 and CD1a in CD14+ monocytes on day 0 and after 7 days of culture in the presence of IL-4 and GM-CSF, as well as of CD25 and Foxp3 in CD3+CD4+, CD3+CD4+CD25–, or CD3+CD4+CD25high purified cell fractions. PBMNC, Peripheral blood mononuclear cells; MACS, magnetic cell sorting; FACS, fluorescence-activated cell sorting; w/wo, with/without. Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2007 American Academy of Allergy, Asthma & Immunology Terms and Conditions

3 Fig 2 Cultured CD4+CD25high Treg cells retain both phenotype and function. A, Proliferation (means ± SDs) of CD4+CD25high and CD4+CD25– T lymphocytes cultured with (gray columns) or without (white columns) autologous DCs (n = 4). B, Foxp3 expression by cultured CD4+CD25high and CD4+CD25– T lymphocytes. C, Proliferation (means ± SDs) of CD4+CD25– T cells to allogeneic stimulation with or without CD4+CD25highFoxp3+ T lymphocytes (n = 4). Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2007 American Academy of Allergy, Asthma & Immunology Terms and Conditions

4 Fig 3 Expansion of antigen-specific CD4+CD25high Foxp3+ T lymphocytes by Der p 1–loaded or SK-loaded autologous DCs. A, Flow-cytometric evaluation of Foxp3 expression. B, Cytokine-producing cells (mean percentages ± SDs) after polyclonal stimulation (n = 3). C and D, Effect of Treg–no Ag, Treg–Der p 1, or Treg-SK on the antigen-induced proliferation of Teff-SK or Teff–Der p1 (n = 5, C; or n = 3, D, respectively). Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2007 American Academy of Allergy, Asthma & Immunology Terms and Conditions

5 Fig 4 Treg–Der p 1, but not Treg-SK, clones suppress the Teff–Der p 1 proliferation. A, Effect of Treg clones on the proliferation of allogeneic-stimulated autologous T lymphocytes. B, Cytokines and Foxp3 expression by clones. C, Inhibition by Treg clones of antigen-induced proliferation of Teff–Der p 1 clones. D, Inhibition (mean percentages ± SDs) by Treg-SK clones of Teff clones proliferation (n = 14). Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2007 American Academy of Allergy, Asthma & Immunology Terms and Conditions

6 Fig 5 Circulating Der p 1–specific CD4+CD25high Treg cells are also present and functionally active in donors with allergy. A, Percentage (means ± SDs) of cytokine-producing cells after polyclonal stimulation in the indicated population (n = 6). B, Effects of Treg–no Ag or Treg–Der p 1 on the antigen-induced proliferation (means ± SDs) of Teff–Der p 1 in Der p 1–sensitive subjects (n = 6). Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2007 American Academy of Allergy, Asthma & Immunology Terms and Conditions

7 Fig 6 Scheme illustrating the in vitro suppression by Treg–Der p 1 cells. DCs present Der p 1 peptides to both Teff–Der p 1 and Treg–Der p 1 cells. Der p 1–induced Teff–Der p 1 cell proliferation is blocked by Der p 1–activated Treg–Der p 1 cells (antigen-specific suppression). Treg-SK cells do not inhibit the Teff–Der p 1 cell proliferation unless they are activated by anti-CD3/anti-CD28 mAbs (nonantigen–specific suppression). TCR, T-cell receptor. Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2007 American Academy of Allergy, Asthma & Immunology Terms and Conditions

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