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The Immunopathogenesis of Cutaneous T-Cell Lymphoma: Abnormal Cytokine Production by Sézary T Cells

The Immunopathogenesis of Cutaneous T-Cell Lymphoma: Abnormal Cytokine Production by Sézary T Cells Abstract For the past 20 years, mycosis fungoides and the Sézary syndrome have been recognized as heterogeneous forms of cutaneous T-cell lymphoma (CTCL).1 The former condition typically evolves slowly through progressive phases of localized cutaneous involvement with plaques and tumors with progression to extracutaneous involvement, generally over a period of years. Malignant cells are usually not detected within the blood in early stages of mycosis fungoides. In contrast, the Sézary syndrome presents with diffuse skin involvement (erythroderma), generalized lymphadenopathy, and the presence of circulating malignant lymphocytes. Thus, the Sézary syndrome is considered to be an advanced form of CTCL characterized by widespread dissemination of the malignant lymphocytes. The neoplastic cells, originally identified in the peripheral blood by Sézary and termed monstrous cells, have maintained the eponym of Sézary cell since that time.2 A hallmark of these cells is the presence of a hyperchromatic nucleus, which, on refined light microscopy and electron microscopy, exhibits deeply References 1. Lutzner M, Edelson R, Schein P, Green I, Kirkpatrick C, Ahmed A. Cutaneous T-cell lymphomas: the Sézary syndrome, mycosis fungoides and related disorders . Ann Intern Med. 1975;83:534-552.Crossref 2. Sézary A, Bouvrain Y. Erythrodermie avec presence de cellules monstreuses dans le derme et dans le sang circulant . Bull Soc Fr Dermatol Syphiligr . 1938;45:254-260. 3. Weiss L, Hu E, Wood G, et al. Clonal rearrangement of T-cell receptor genes in mycosis fungoides and dermatopathic lymphadenopathy . N Engl J Med. 1985;313:539-544.Crossref 4. Vowels BR, Cassin M, Vonderheid E, Rook AH. Aberrant cytokine production by Sézary syndrome patients: cytokine secretion pattern resembles murine Th 2 cells . J Invest Dermatol. 1992;99:90-94.Crossref 5. Haynes BF, Bunn P, Mann D, Thomas C. Cell surface differentiation antigens of the malignant T cell in Sézary syndrome and mycosis fungoides . J Clin Invest. 1981;67:523-530.Crossref 6. Broder S, Edelson RL, Lutzner M, et al. The Sézary syndrome: a malignant proliferation of helper T cells . J Clin Invest. 1976;58: 1297-1306.Crossref 7. Vowels BR, Lessin S, Cassin M, Rook AH. Quantitative polymerase chain reaction analysis of interleukin 4 and interleukin 5 demonstrates aberrant cytokine production in Sézary syndrome . J Invest Dermatol. 1992;98:615.Crossref 8. Dummer R, Kohl O, Gillessen J, Kagi M, Burg G. Peripheral blood mononuclear cells in patients with nonleukemic cutaneous T-cell lymphoma: reduced proliferation and preferential secretion of a T helper-2—like cytokine pattern on stimulation . Arch Dermatol. 1992;129:433-436.Crossref 9. Mosmann TR, Cherwinski H, Bond MW, Giedlen MA, Coffman RL. Two types of murine helper T cell clone, I: definition according to profiles of lymphokine activities and secreted proteins . J Immunol. 1986;136:2348-2357. 10. Rotteveel FTM, Kokkelink I, vanLier RAW, et al. Clonal analysis of functionally distinct human CD4+ T cell subsets . J Exp Med. 1988;168:1659-1673.Crossref 11. Umetsu DT, Jabara HH, DeKruyff RH, Abbas AK, Abrams JS, Geha RS. Functional heterogeneity among human inducer T cell clones . J Immunol. 1988;140:4211-4216. 12. Nickoloff BJ, Griffiths CEM, Baadsgaard O, Voorhees JJ, Hanson CA, Cooper KD. Markedly diminished epidermal keratinocyte expression of intercellular adhesion molecule-1 (ICAM-1) in Sézary syndrome . JAMA . 1989;261:2217-2221.Crossref 13. Griffiths CEM, Voorhees JJ, Nickoloff BJ. Characterization of intercellular adhesion molecule-1 and HLA-DR expression in normal and inflamed skin: modulation by recombinant gamma interferon and tumor necrosis factor . J Am Acad Dermatol. 1989;20:617-629.Crossref 14. Peleman R, Wu J, Rargeas C, Delespesse G. Recombinant interleukin 4 suppresses the production of interferon gamma by human mononuclear cells . J Exp Med. 1989;170:1751-1756.Crossref 15. Gajewski TF, Fitch FW. Anti-proliferative effect of IFN γ in immune regulation, I: IFN γ inhibits the proliferation of TH2 but not TH1 murine CTL clones . J Immunol. 1988;140:4245-4252. 16. Kawakami Y, Custer MC, Rosenberg SA, Lotze MT. IL-4 regulates IL-2 induction of lymphokine-activated killer activity from human lymphocytes . J Immunol. 1989;142:3452-3461. 17. Trinchieri G. Biology of natural killer cells . Adv Immunol. 1989;47:187-376. 18. Kaplan EH, Rosen ST, Norris DB, Roenigk HH, Saks SR, Bunn PA. Phase II study of recombinant human interferon gamma for treatment of cutaneous T-cell lymphoma . J Natl Cancer Inst. 1990;82:208-212.Crossref 19. Olsen EA, Rosen ST, Vollmer RT, et al. Interferon alfa-2a in the treatment of cutaneous T-cell lymphoma . J Am Acad Dermatol. 1989;20:395-407.Crossref 20. Edelson R, Berger C, Gasparro F, et al. Treatment of cutaneous T-cell lymphoma by extracorporeal photochemotherapy: preliminary results . N Engl J Med. 1987;316:297-303.Crossref 21. Romagnani S. Induction of Th 1 and Th 2 responses: a key role for the natural immune response? Immunol Today . 1992;13:379-381.Crossref 22. Vowels BR, Cassin M, Boufal M, Walsh LJ, Rook AH. Extracorporeal photochemotherapy induces the production of tumor necrosis factor α by monocytes: implications for the treatment of cutaneous T-cell lymphoma and systemic sclerosis . J Invest Dermatol. 1992;98:686-692.Crossref 23. Rook AH, Prystowsky MB, Cassin M, Boufal M, Lessin SR. Combined therapy of the Sézary syndrome with extracorporeal photochemotherapy and low dose interferon alfa: clinical, molecular, and immunologic observations . Arch Dermatol. 1991;127:1535-1540.Crossref 24. Cohen JH, Lessin SR, Vowels BR, Benoit B, Witmer WK, Rook AH. The sign of Leser-Trelat in association with Sézary syndrome: simultaneous disappearance of seborrheic keratoses and malignant T-cell clone during combined therapy with photopheresis and interferon alfa . Arch Dermatol. In press. 25. Edelson RL. Photopheresis: a clinically relevant immunobiologic response modifier . Ann N Y Acad Sci. 1991;636:154-164.Crossref 26. Bos JD, Wierenga EA, Sillevis Smitt JH, et al. Immune dysregulation in atopic eczema . Arch Dermatol. 1992;128:1509-1512.Crossref 27. Renz H, Jujo K, Bradley KL, et al. Enhanced IL-4 production and IL-4 receptor expression in atopic dermatitis and their modulation by interferon gamma . J Invest Dermatol. 1992;99:403-408.Crossref 28. Robinson DS, Hamid Q, Ying S, et al. Predominant Th 2-like bronchoalveolar T-lymphocyte population in atopic asthma . N Engl J Med. 1992;326:298-304.Crossref 29. Mosmann TR. Cytokine secretion patterns and cross-regulation of T-cell subsets . Immunol Res. 1991;10:183-188.Crossref 30. Del Prete G, Tiri A, Maggi E, et al. Defective in vitro production of gamma interferon and tumor necrosis factor alfa by circulating T cells from patients with the hyper-immunoglobulin E syndrome . J Clin Invest. 1989;84:1830-1835.Crossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Dermatology American Medical Association

The Immunopathogenesis of Cutaneous T-Cell Lymphoma: Abnormal Cytokine Production by Sézary T Cells

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Publisher
American Medical Association
Copyright
Copyright © 1993 American Medical Association. All Rights Reserved.
ISSN
0003-987X
eISSN
1538-3652
DOI
10.1001/archderm.1993.01680250098016
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Abstract

Abstract For the past 20 years, mycosis fungoides and the Sézary syndrome have been recognized as heterogeneous forms of cutaneous T-cell lymphoma (CTCL).1 The former condition typically evolves slowly through progressive phases of localized cutaneous involvement with plaques and tumors with progression to extracutaneous involvement, generally over a period of years. Malignant cells are usually not detected within the blood in early stages of mycosis fungoides. In contrast, the Sézary syndrome presents with diffuse skin involvement (erythroderma), generalized lymphadenopathy, and the presence of circulating malignant lymphocytes. Thus, the Sézary syndrome is considered to be an advanced form of CTCL characterized by widespread dissemination of the malignant lymphocytes. The neoplastic cells, originally identified in the peripheral blood by Sézary and termed monstrous cells, have maintained the eponym of Sézary cell since that time.2 A hallmark of these cells is the presence of a hyperchromatic nucleus, which, on refined light microscopy and electron microscopy, exhibits deeply References 1. Lutzner M, Edelson R, Schein P, Green I, Kirkpatrick C, Ahmed A. Cutaneous T-cell lymphomas: the Sézary syndrome, mycosis fungoides and related disorders . Ann Intern Med. 1975;83:534-552.Crossref 2. Sézary A, Bouvrain Y. Erythrodermie avec presence de cellules monstreuses dans le derme et dans le sang circulant . Bull Soc Fr Dermatol Syphiligr . 1938;45:254-260. 3. Weiss L, Hu E, Wood G, et al. Clonal rearrangement of T-cell receptor genes in mycosis fungoides and dermatopathic lymphadenopathy . N Engl J Med. 1985;313:539-544.Crossref 4. Vowels BR, Cassin M, Vonderheid E, Rook AH. Aberrant cytokine production by Sézary syndrome patients: cytokine secretion pattern resembles murine Th 2 cells . J Invest Dermatol. 1992;99:90-94.Crossref 5. Haynes BF, Bunn P, Mann D, Thomas C. Cell surface differentiation antigens of the malignant T cell in Sézary syndrome and mycosis fungoides . J Clin Invest. 1981;67:523-530.Crossref 6. Broder S, Edelson RL, Lutzner M, et al. The Sézary syndrome: a malignant proliferation of helper T cells . J Clin Invest. 1976;58: 1297-1306.Crossref 7. Vowels BR, Lessin S, Cassin M, Rook AH. Quantitative polymerase chain reaction analysis of interleukin 4 and interleukin 5 demonstrates aberrant cytokine production in Sézary syndrome . J Invest Dermatol. 1992;98:615.Crossref 8. Dummer R, Kohl O, Gillessen J, Kagi M, Burg G. Peripheral blood mononuclear cells in patients with nonleukemic cutaneous T-cell lymphoma: reduced proliferation and preferential secretion of a T helper-2—like cytokine pattern on stimulation . Arch Dermatol. 1992;129:433-436.Crossref 9. Mosmann TR, Cherwinski H, Bond MW, Giedlen MA, Coffman RL. Two types of murine helper T cell clone, I: definition according to profiles of lymphokine activities and secreted proteins . J Immunol. 1986;136:2348-2357. 10. Rotteveel FTM, Kokkelink I, vanLier RAW, et al. Clonal analysis of functionally distinct human CD4+ T cell subsets . J Exp Med. 1988;168:1659-1673.Crossref 11. Umetsu DT, Jabara HH, DeKruyff RH, Abbas AK, Abrams JS, Geha RS. Functional heterogeneity among human inducer T cell clones . J Immunol. 1988;140:4211-4216. 12. Nickoloff BJ, Griffiths CEM, Baadsgaard O, Voorhees JJ, Hanson CA, Cooper KD. Markedly diminished epidermal keratinocyte expression of intercellular adhesion molecule-1 (ICAM-1) in Sézary syndrome . JAMA . 1989;261:2217-2221.Crossref 13. Griffiths CEM, Voorhees JJ, Nickoloff BJ. Characterization of intercellular adhesion molecule-1 and HLA-DR expression in normal and inflamed skin: modulation by recombinant gamma interferon and tumor necrosis factor . J Am Acad Dermatol. 1989;20:617-629.Crossref 14. Peleman R, Wu J, Rargeas C, Delespesse G. Recombinant interleukin 4 suppresses the production of interferon gamma by human mononuclear cells . J Exp Med. 1989;170:1751-1756.Crossref 15. Gajewski TF, Fitch FW. Anti-proliferative effect of IFN γ in immune regulation, I: IFN γ inhibits the proliferation of TH2 but not TH1 murine CTL clones . J Immunol. 1988;140:4245-4252. 16. Kawakami Y, Custer MC, Rosenberg SA, Lotze MT. IL-4 regulates IL-2 induction of lymphokine-activated killer activity from human lymphocytes . J Immunol. 1989;142:3452-3461. 17. Trinchieri G. Biology of natural killer cells . Adv Immunol. 1989;47:187-376. 18. Kaplan EH, Rosen ST, Norris DB, Roenigk HH, Saks SR, Bunn PA. Phase II study of recombinant human interferon gamma for treatment of cutaneous T-cell lymphoma . J Natl Cancer Inst. 1990;82:208-212.Crossref 19. Olsen EA, Rosen ST, Vollmer RT, et al. Interferon alfa-2a in the treatment of cutaneous T-cell lymphoma . J Am Acad Dermatol. 1989;20:395-407.Crossref 20. Edelson R, Berger C, Gasparro F, et al. Treatment of cutaneous T-cell lymphoma by extracorporeal photochemotherapy: preliminary results . N Engl J Med. 1987;316:297-303.Crossref 21. Romagnani S. Induction of Th 1 and Th 2 responses: a key role for the natural immune response? Immunol Today . 1992;13:379-381.Crossref 22. Vowels BR, Cassin M, Boufal M, Walsh LJ, Rook AH. Extracorporeal photochemotherapy induces the production of tumor necrosis factor α by monocytes: implications for the treatment of cutaneous T-cell lymphoma and systemic sclerosis . J Invest Dermatol. 1992;98:686-692.Crossref 23. Rook AH, Prystowsky MB, Cassin M, Boufal M, Lessin SR. Combined therapy of the Sézary syndrome with extracorporeal photochemotherapy and low dose interferon alfa: clinical, molecular, and immunologic observations . Arch Dermatol. 1991;127:1535-1540.Crossref 24. Cohen JH, Lessin SR, Vowels BR, Benoit B, Witmer WK, Rook AH. The sign of Leser-Trelat in association with Sézary syndrome: simultaneous disappearance of seborrheic keratoses and malignant T-cell clone during combined therapy with photopheresis and interferon alfa . Arch Dermatol. In press. 25. Edelson RL. Photopheresis: a clinically relevant immunobiologic response modifier . Ann N Y Acad Sci. 1991;636:154-164.Crossref 26. Bos JD, Wierenga EA, Sillevis Smitt JH, et al. Immune dysregulation in atopic eczema . Arch Dermatol. 1992;128:1509-1512.Crossref 27. Renz H, Jujo K, Bradley KL, et al. Enhanced IL-4 production and IL-4 receptor expression in atopic dermatitis and their modulation by interferon gamma . J Invest Dermatol. 1992;99:403-408.Crossref 28. Robinson DS, Hamid Q, Ying S, et al. Predominant Th 2-like bronchoalveolar T-lymphocyte population in atopic asthma . N Engl J Med. 1992;326:298-304.Crossref 29. Mosmann TR. Cytokine secretion patterns and cross-regulation of T-cell subsets . Immunol Res. 1991;10:183-188.Crossref 30. Del Prete G, Tiri A, Maggi E, et al. Defective in vitro production of gamma interferon and tumor necrosis factor alfa by circulating T cells from patients with the hyper-immunoglobulin E syndrome . J Clin Invest. 1989;84:1830-1835.Crossref

Journal

Archives of DermatologyAmerican Medical Association

Published: Apr 1, 1993

References