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Vol. 213, No. 2, 2006
Issue release date: August 2006
Dermatology 2006;213:111–117
(DOI:10.1159/000093849)

Identification of Lesional CD4+ CD25+ Foxp3+ Regulatory T Cells in Psoriasis

Bovenschen H.J. · van Vlijmen-Willems I.M.J.J. · van de Kerkhof P.C.M. · van Erp P.E.J.
Department of Dermatology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands

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Abstract

Background: Depletion of CD4+ CD25+ Foxp3+ naturally occurring regulatory T cells (Treg) induces autoimmune phenomena. These cells have not yet been fully characterized in the skin of psoriatic patients. Objectives: To prove that the Zenon immunofluorescent labeling technique is suitable for the demonstration of co-localization of T-cell markers and in particular to show the distribution of Treg in psoriatic skin. Methods: In biopsies derived from normal and psoriatic skin, CD4+ CD25+, CD4+ CD45RO+, CD8+ CD25+, CD8+ CD45RO+ and CD4+ CD25+ Foxp3+ cells in the dermis and in the epidermis were immunophenotyped, using a quantitative immunofluorescent labeling technique (Zenon), analyzed and compared using image analysis. Results:The immunofluorescent labeling technique was shown to be an easy and reliable tool to demonstrate co-localization of T-cell markers. In psoriasis, all pathogenic T-cell subsets (CD4+ CD25+, CD4+ CD45RO+, CD8+ CD25+ and CD8+ CD45RO+ cells) were significantly increased in the dermis and in the epidermis, as compared to normal skin (all p < 0.05). Using this labeling technique we were able to reveal CD4+ CD25+ Foxp3+ Treg in psoriatic dermis, but not in the dermis of normal skin (p < 0.0001). Conclusions:The Zenon immunofluorescence technique in combination with image analysis is suitable for the demonstration of co-localization of T-cell markers in tissue. Increased numbers of pathogenic T cells (CD4+ CD25+, CD4+ CD45RO+, CD8+ CD25+ and CD8+ CD45RO+) were shown in the dermis and epidermis, whereas CD4+ CD25+ Foxp3+ Treg were identified in psoriatic skin with a predilection for the upper dermis.



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References

  1. Krueger JG: The immunologic basis for the treatment of psoriasis with new biologic agents. J Am Acad Dermatol 2002;46:1–23.
  2. Gudjonsson JE, Johnston A, Sigmundsdottir H, Valdimarsson H: Immunopathogenic mechanisms in psoriasis. Clin Exp Immunol 2004;135:1–8.
  3. Mommers JM, van Rossum MM, van Erp PE, van de Kerkhof PC: Changes in keratin 6 and keratin 10 (co-)expression in lesional and symptomless skin of spreading psoriasis. Dermatology 2000;201:15–20.
  4. Castelijns FA, Gerritsen MJ, van Erp PE, van de Kerkhof PC: Cell-kinetic evidence for increased recruitment of cycling epidermal cells in psoriasis: the ratio of histone and Ki-67 antigen expression is constant. Dermatology 2000;201:105–110.
  5. Valdimarsson H, Baker BS, Jonsdottir I, Fry L: Psoriasis: a disease of abnormal proliferation induced by T lymphocytes. Immunol Today 1986;7:256–259.
  6. Prinz JC, Gross B, Vollmer S, et al: T cell clones from psoriasis skin lesions can promote keratinocyte proliferation in vitro. Eur J Immunol 1994;24:593–598.
  7. Bovenschen HJ, Seyger MMB, van de Kerkhof PCM: Plaque psoriasis versus atopic dermatitis and lichen planus: a comparison for lesional T-cell subsets, epidermal proliferation and differentiation. Br J Dermatol2005;153:72–78.
  8. Bach J-F: Regulatory T cells under scrutiny. Nat Rev Immunol 2003;3:189–198.
  9. Sakaguchi S, Sakaguchi N, Asano M, Itoh M, Toda M: Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25): breakdown of a single mechanism of self-tolerance causes various autoimmune diseases. J Immunol 1995;155:1151–1164.
  10. Asano M, Toda M, Sakaguchi N, Sakaguchi S: Autoimmune disease as a consequence of developmental abnormality of a T cell subpopulation. J Exp Med 1996;184:387–396.
  11. Takahashi T, Kuniyasu Y, Toda M, et al: Immunologic self-tolerance maintained by CD25+CD4+ naturally anergic and suppressive T cells: induction of autoimmune disease by breaking their anergic/suppressive state. Int Immunol 1998;10:1969–1980.
  12. Thornton AM, Shevach EM: CD4+CD25+ immunoregulatory T cells suppress polyclonal T cell activation in vitro by inhibiting interleukin 2 production. J Exp Med 1998;188:287–296.
  13. Dieckmann D, Plottner H, Berchtold S, Berger T, Schuler G: Ex vivo isolation and characterization of CD4(+)CD25(+) T cells with regulatory properties from human blood. J Exp Med 2001;193:1303–1310.
  14. Levings MK, Sangregorio R, Roncarolo MG: Human CD25(+)CD4(+) T regulatory cells suppress naive and memory T cell proliferation and can be expanded in vitro without loss of function. J Exp Med 2001;193:1295–1302.
  15. Bluestone JA, Abbas AK: Natural versus adaptive regulatory T cells. Nat Rev Immunol 2003;3:253–257.
  16. Pop SM, Wong CP, Culton DA, Clarke SH, Tisch R: Single cell analysis shows decreasing FoxP3 and TGFbeta1 coexpressing CD4+CD25+ regulatory T cells during autoimmune diabetes. J Exp Med 2005;201:1333–1346.
  17. Viglietta V, Baecher-Allan C, Weiner HL, Hafler DA: Loss of functional suppression by CD4+CD25+ regulatory T cells in patients with multiple sclerosis. J Exp Med 2004;199:971–979.
  18. Crispin JC, Martinez A, Alcocer-Varela J: Quantification of regulatory T cells in patients with systemic lupus erythematosus. J Autoimmun2003;21:273–276.
  19. Miyara M, Amoura Z, Parizot C, et al: Global natural regulatory T cell depletion in active systemic lupus erythematosus. J Immunol 2005;175:8392–8400.
  20. Sugiyama H, Gyulai R, Toichi E, et al: Dysfunctional blood and target tissue CD4+CD25+ high regulatory T cells in psoriasis: mechanism underlying unrestrained pathogenic effector T cell proliferation. J Immunol 2005;174:164–173.
  21. Wildin RS, Smyk-Pearson S, Filipovich AH: Clinical and molecular features of the immunodysregulation, polyendocrinopathy, enteropathy, X linked (IPEX) syndrome. J Med Genet 2002;39:537–545.
  22. Gambineri E, Torgerson TR, Ochs HD: Immune dysregulation, polyendocrinopathy, enteropathy, and X-linked inheritance (IPEX), a syndrome of systemic autoimmunity caused by mutations of FOXP3, a critical regulator of T-cell homeostasis. Curr Opin Rheumatol2003;15:430–435.
  23. Ramsdell F: Foxp3 and natural regulatory T cells: key to a cell lineage? Immunity 2003;19:165–168.
  24. Nieves DS, Phipps RP, Pollock SJ, et al: Dermatologic and immunologic findings in the immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome. Arch Dermatol 2004;140:466–472.
  25. Schwartz RH: Natural regulatory T cells and self-tolerance.Nat Immunol2005;6:327–330.
  26. Sakaguchi S: Naturally arising Foxp3-expressing CD25+CD4+ regulatory T cells in immunological tolerance to self and non-self. Nat Immunol2005;6:345–352.
  27. Nielsen J, Holm TL, Claesson MH: CD4+CD25+ regulatory T cells. II. Origin, disease models and clinical aspects. APMIS2004;112:642–650.
  28. Fontenot JD, Rudensky AY: A well adapted regulatory contrivance: regulatory T cell development and the forkhead family transcription factor Foxp3. Nat Immunol 2005;6:331–337.
  29. Hori S, Nomura T, Sakaguchi S: Control of regulatory T cell development by the transcription factor Foxp3. Science 2003;299:1057–1061.
  30. Van Duijnhoven MW, van de Kerkhof PC, Pasch MC, Muys L, van Erp PE: The combination of the Zenon labeling technique and microscopic image analysis to study cell populations in normal and psoriatic epidermis. J Cutan Pathol 2005;32:212–219.
  31. Vissers WH, Arndtz CH, Muys L, van Erp PE, de Jong EM, van de Kerkhof PC: Memory effector (CD45RO+) and cytotoxic (CD8+) T cells appear early in the margin zone of spreading psoriatic lesions in contrast to cells expressing natural killer receptors, which appear late. Br J Dermatol 2004;150:852–859.
  32. Guilhou J: Immunopathogenesis of psoriasis: news in an old concept. Dermatology 1998;197:310–312.
  33. Bradford JA, Buller G, Suter M, Ignatius M, Beechem JM: Fluorescence-intensity multiplexing: simultaneous seven-marker, two-color immunophenotyping using flow cytometry. Cytometry A 2004;61:142–152.
  34. Martin K, Hart C, Liu J, Leung WY, Patton WF: Simultaneous trichromatic fluorescence detection of proteins on Western blots using an amine-reactive dye in combination with alkaline phosphatase- and horseradish peroxidase-antibody conjugates. Proteomics 2003;3:1215–1227.
  35. Verhagen J, Akdis M, Traidl-Hoffmann C, et al: Absence of T-regulatory cell expression and function in atopic dermatitis skin. J Allergy Clin Immunol 2006;117:176–183.
  36. Kursar M, Bonhagen K, Fensterle J, et al: Regulatory CD4+CD25+ T cells restrict memory CD8+ T cell responses. J Exp Med 2002;196:1585–1592.
  37. Bovenschen HJ, Vissers WH, Seyger MM, van de Kerkhof PC: Selective persistence of dermal CD8+ T cells in lesional plaque psoriasis after clobetasol-17 propionate treatment. Acta Derm Venereol 2005;85:113–117.
  38. Kohlmann WM, Urban W, Sterry W, Foerster J: Correlation of psoriasis activity with abundance of CD25+CD8+ T cells: conditions for cloning T cells from psoriatic plaques. Exp Dermatol 2004;13:607–612.


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