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Immunoregulatory Events in the Skin of Patients With Cutaneous T-Cell Lymphoma

Immunoregulatory Events in the Skin of Patients With Cutaneous T-Cell Lymphoma Abstract Background: Involved skin of patients with cutaneous T-cell lymphoma, mycosis fungoides type, contains an increased number of bone marrow—derived epidermal cells that express class II major histocompatibility complex molecules and an infiltrate of both activated non-malignant and malignant T cells. However, the mechanism by which the T cells achieve and maintain their activated state is uncertain. The aim of this article is, therefore, to review recent studies from the literature dealing with immunoregulatory events in patients with mycosis fungoides and Sézary syndrome. Observations: The nonmalignant T cells seem to be activated through the T-cell receptor by lesional epidermal CD1a+CD36+ macrophagelike cells that, on a cell per cell basis, are more potent antigen-presenting cells than normal CD1a+ Langerhans' cells present in uninvolved epidermis. In contrast, the malignant T cells have different activation requirements, because they can only be stimulated through antigen independent pathways, such as CDw60, CD28, and CD2. The malignant T cells produce T-helper (Th)-2 cytokines, and because interferon gamma (IFN-γ)-producing Thl cells are present in the early lesions of mycosis fungoides, nonmalignant tumor-infiltrating T cells may represent Thl cells. Because Thl cytokines counteract Th2 cytokines, tumor-infiltrating T cells may potentially have the capacity to downregulate the growth of the malignant cells. Conclusion: The balance between progression vs remission in mycosis fungoides is related to complex interactions between the malignant T cells, nonmalignant T cells, and hyperstimulative antigen-presenting cells present within the skin.(Arch Dermatol. 1996;132:554-561) References 1. Weinstock MA, Horm JW. Mycosis fungoides in the United States: increasing incidence and descriptive epidemiology . JAMA . 1988;260:42-46.Crossref 2. Sterry W, Mielke V. CD4+ cutaneous T-cell lymphomas show the phenotype of helper/inducer T cells (CD45RA-, CDw29+) . J Invest Dermatol. 1989;93: 413-416.Crossref 3. Ralfkiaer E, Wollf-Sneedorff A, Thomsen K, Geisler C, Vejlsgaard G. T-cell receptor gamma delta-positive peripheral T-cell lymphomas presenting in the skin: a clinical, histological and immunophenotypic study . Exp Dermatol. 1992; 1:31-36.Crossref 4. Fujiwara Y, Abe Y, Kuyama M, et al. CD8+ cutaneous T-cell lymphoma with pagetoid epidermotropism and angiocentric and angiodestructive infiltration . Arch Dermatol. 1990;126:801-804.Crossref 5. Ralfkiaer E. Immunohistological and genotypic studies of cutaneous malignant lymphomas compared with benign cutaneous conditions and cutaneous pseudolymphomas. Copenhagen, Denmark: University of Copenhagen; 1989. Thesis. 6. Slater DN. Cutaneous lymphoproliferative disorders: an assessment of recent investigative techniques . Br J Dermatol. 1991;124:309-323.Crossref 7. Ralfkiaer E, Wollf-Sneedorff A, Vejlsgaard G. Use of antibodies against the variable regions of the T-cell receptor alpha/beta heterodimer for the study of cutaneous T-cell lymphomas . Br J Dermatol. 1991;125:409-412.Crossref 8. Jensen JR, Thestrup-Pedersen K, Zachariae H, Sogaard H. Cyclosporin A therapy for mycosis fungoides . Arch Dermatol. 1987;123:160-163.Crossref 9. Thomsen K, Wantzin GL. Extracutaneous spreading with fatal outcome of mycosis fungoides in a patient treated with cyclosporin A: a word of caution . Dermatologica. 1987;174:236-238.Crossref 10. Crane GA, Variakojis D, Rosen ST, Sands AM, Roenigk HHJ. Cutaneous T-cell lymphoma in patients with human immunodeficiency virus infections . Arch Dermatol. 1991;127:989-994.Crossref 11. Penn I. Cancer in the immunosuppressed organ recipient . Transplant Proc. 1991;23:1771-1772. 12. Olsen EA, Delzell E, Jegasothy BV. Second malignancies in cutaneous T cell lymphoma . 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Cytokine loops involving interferongamma and IP-10, a cytokine chemotactic for CD4+ lymphocytes: an explanation for the epidermotropism of cutaneous T-cell lymphoma? J Am Soc Hematol. 1995;86:651-658. 76. Ishii T, Walsh LJ, Seymour GJ, Powell RN. Modulation of Langerhans cell surface antigen expression by recombinant cytokines . J Oral Pathol Med. 1990; 19:355-359.Crossref 77. Walsh LJ, Parry A, Scholes A, Seymour GJ. Modulation of CD4 antigen expression on human gingival Langerhans cells by gamma interferon . Clin Exp Immunol. 1987;70:379-385. 78. Berman B, Duncan MR, Smith B, Ziboh VA, Palladino M. Interferon enhancement of HLA-DR antigen expression on epidermal Langerhans cells . J Invest Dermatol. 1985;84:54-58.Crossref 79. Barker JN, Allen MH, MacDonald DM. The effect of in vivo interferon gamma on the distribution of LFA-1 and ICAM-1 in normal human skin . J Invest Dermatol. 1989;93:439-442.Crossref 80. Wayner E, Hoffstrom B, Pittlekow M. T Lymphocyte adhesion to keratinocytes: cooperative role for the integrin receptor alpha 3 beta 1 and E-cadherin . J Invest Dermatol. 1994;102:524. 81. Sterry W, Mielke V, Konter U, Kellner I, Boehncke WH. Role of beta 1-integrins in epidermotropism of malignant T cells . Am J Pathol. 1992;141:855-860. 82. Picker LJ, Michie SA, Rott LS, Butcher EC. A unique phenotype of skin-associated lymphocytes in humans: preferential expression of the HECA-452 epitope by benign and malignant T cells at cutaneous sites . Am J Pathol. 1990;136:1053-1068. 83. Vejlsgaard GL, Ralfkiaer E, Avnstorp C, Czajkowski M, Marlin SD, Rothlein R. Kinetics and characterization of intercellular adhesion molecule-1 (ICAM-1) expression on keratinocytes in various inflammatory skin lesions and malignant cutaneous lymphomas . J Am Acad Dermatol. 1989;20:782-790.Crossref 84. Nickoloff BJ, Griffiths CE, Baadsgaard O, Voorhees JJ, Hanson CA, Cooper KD. 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Immunoregulatory Events in the Skin of Patients With Cutaneous T-Cell Lymphoma

Hansen, Erik R.
Archives of Dermatology , Volume 132 (5) – May 1, 1996
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American Medical Association
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Copyright © 1996 American Medical Association. All Rights Reserved.
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0003-987X
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1538-3652
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10.1001/archderm.1996.03890290088012
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Abstract

Abstract Background: Involved skin of patients with cutaneous T-cell lymphoma, mycosis fungoides type, contains an increased number of bone marrow—derived epidermal cells that express class II major histocompatibility complex molecules and an infiltrate of both activated non-malignant and malignant T cells. However, the mechanism by which the T cells achieve and maintain their activated state is uncertain. The aim of this article is, therefore, to review recent studies from the literature dealing with immunoregulatory events in patients with mycosis fungoides and Sézary syndrome. Observations: The nonmalignant T cells seem to be activated through the T-cell receptor by lesional epidermal CD1a+CD36+ macrophagelike cells that, on a cell per cell basis, are more potent antigen-presenting cells than normal CD1a+ Langerhans' cells present in uninvolved epidermis. In contrast, the malignant T cells have different activation requirements, because they can only be stimulated through antigen independent pathways, such as CDw60, CD28, and CD2. The malignant T cells produce T-helper (Th)-2 cytokines, and because interferon gamma (IFN-γ)-producing Thl cells are present in the early lesions of mycosis fungoides, nonmalignant tumor-infiltrating T cells may represent Thl cells. Because Thl cytokines counteract Th2 cytokines, tumor-infiltrating T cells may potentially have the capacity to downregulate the growth of the malignant cells. Conclusion: The balance between progression vs remission in mycosis fungoides is related to complex interactions between the malignant T cells, nonmalignant T cells, and hyperstimulative antigen-presenting cells present within the skin.(Arch Dermatol. 1996;132:554-561) References 1. Weinstock MA, Horm JW. Mycosis fungoides in the United States: increasing incidence and descriptive epidemiology . JAMA . 1988;260:42-46.Crossref 2. Sterry W, Mielke V. CD4+ cutaneous T-cell lymphomas show the phenotype of helper/inducer T cells (CD45RA-, CDw29+) . J Invest Dermatol. 1989;93: 413-416.Crossref 3. Ralfkiaer E, Wollf-Sneedorff A, Thomsen K, Geisler C, Vejlsgaard G. T-cell receptor gamma delta-positive peripheral T-cell lymphomas presenting in the skin: a clinical, histological and immunophenotypic study . Exp Dermatol. 1992; 1:31-36.Crossref 4. Fujiwara Y, Abe Y, Kuyama M, et al. CD8+ cutaneous T-cell lymphoma with pagetoid epidermotropism and angiocentric and angiodestructive infiltration . Arch Dermatol. 1990;126:801-804.Crossref 5. Ralfkiaer E. Immunohistological and genotypic studies of cutaneous malignant lymphomas compared with benign cutaneous conditions and cutaneous pseudolymphomas. Copenhagen, Denmark: University of Copenhagen; 1989. Thesis. 6. Slater DN. Cutaneous lymphoproliferative disorders: an assessment of recent investigative techniques . Br J Dermatol. 1991;124:309-323.Crossref 7. Ralfkiaer E, Wollf-Sneedorff A, Vejlsgaard G. Use of antibodies against the variable regions of the T-cell receptor alpha/beta heterodimer for the study of cutaneous T-cell lymphomas . Br J Dermatol. 1991;125:409-412.Crossref 8. Jensen JR, Thestrup-Pedersen K, Zachariae H, Sogaard H. Cyclosporin A therapy for mycosis fungoides . Arch Dermatol. 1987;123:160-163.Crossref 9. Thomsen K, Wantzin GL. Extracutaneous spreading with fatal outcome of mycosis fungoides in a patient treated with cyclosporin A: a word of caution . Dermatologica. 1987;174:236-238.Crossref 10. Crane GA, Variakojis D, Rosen ST, Sands AM, Roenigk HHJ. Cutaneous T-cell lymphoma in patients with human immunodeficiency virus infections . Arch Dermatol. 1991;127:989-994.Crossref 11. Penn I. Cancer in the immunosuppressed organ recipient . Transplant Proc. 1991;23:1771-1772. 12. Olsen EA, Delzell E, Jegasothy BV. Second malignancies in cutaneous T cell lymphoma . 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Journal

Archives of Dermatology – American Medical Association

Published: May 1, 1996

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