Abstract
We review our data suggesting that interactions between reactive and malignant T cells in lesions of cutaneous T cell lymphoma (CTCL) may play a role in the biology of CTCL. T cell receptor gene rearrangement (TCRGR) analysis allows the identification of the malignant clone on the basis of the unique size of the TCR gene fragments after enzyme digestion. We identified the malignant clone by TCRGR analysis of DNA extracts from lesionai skin of patients with CTCL, mycosis fungoides type, and compared the TCRGR pattern to that of T cell clones established from lesionai skin of the same patients. We found that each clone demonstrated a TCRGR pattern unique from the others and different from that of the malignant clone identified in the lesion. These data established that a polyclonal population of tumor infiltrating lymphocytes (TEL) are present in the lesion (and potentially regulating the malignant clone), and also suggest that the malignant clone and the TIL’s may have different activation requirements. Intralesional activation of malignant or TIL clones may be induced by abnormal antigen presenting cells (APC’s) in the lesion. We showed that lesionai CDla+ cells (Langerhans cells;LC), purified on immunomagnetic beads, demonstrated ultrastructural abnormalities such as hyperconvoluted nuclei and significant melanophagocytosis. In addition, these LC demonstrated strong expression of CD36, CD11c and CD1c, markers normally more highly expressed on dermal perivascular dendritic cells, in addition to expression of molecules present on normal LC, such as HLA-DR and CDla. Although these modulated LC are hyperstimulatory for autologous T cells, it is not yet clear whether they are stimulating the malignant clone or the TIL’s in the lesion. The balance between progression versus indolence may be related to complex interactions between the cells of the malignant clone, TIL’s, and APC’s.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Abrams JT, S Lessin, SK Ghosh, et al., 1991a. A clonal CD4-positive T-cell line established from the blood of a patient with Sézary syndrome. J. Invest. Dermatol., 96: 31–37.
Abrams JT, SR Lessin, SK Ghosh, et al., 1991b. Malignant and nonmalignant T cell lines from human T cell lymphotropic virus type I-negative patients with Sezary syndrome. J. Immunol., 146: 1455–1462.
Baadsgaard O, ER Hansen, V Ho, et al., 1988. Activation of T cells from Sezary patients can occur through both antigen dependent and independent pathways. J. Invest. Dermatol., 91: 386.
Basham TY, BJ Nickoloff, TC Merigan and VB Morhenn, 1984. Recombinant gamma interferon induces HLA-DR expression on cultured keratinocytes. J. Invest. Dermatol., 83: 88–90.
Braverman IM, S Klein and A Grant, 1987. Electron microscopic and immunolabeling studies of the lesionai and normal skin of patients with mycosis fungoides treated by total body electron beam irradiation. J. Am. Acad. Dermatol., 16: 61–74.
Cattoretti G, E Berti, A Mancuso et al., 1987. An MHC class I related family of antigens with widespread distribution on resting and activated cells. In: AJ McMichael, PCL Beverley, W Gilks et al., Eds., Leucocyte Typing III. White Cell Differentiation Antigens, Oxford, Oxford University Press, pp. 89–91.
Edelson R, C Berger, F Gasparro, et al., 1987. Treatment of cutaneous T-cell lymphoma by extracorporeal photochemotherapy. Preliminary results. N. Engl. J. Med., 316: 297–303.
Hansen ER, O Baadsgaard, S Lisby, KD Cooper, K Thomsen and GL Wantzin, 1988. Epidermal cells from mycosis fungoides demonstrate MHC-Class II dependent activation of the CD4+CD8-lymphocyte subset. J. Invest. Dermatol., 91: 386A.(Abstract)
Hansen ER, O Baadsgaard, S Lisby, KD Cooper, K Thomsen and GL Vejlsgaard, 1990. Cutaneous T-cell lymphoma lesionai epidermal cells activate autologous CD4+ T lymphocytes: Involvement of both CD1+0KM5 + and CDl +0KM5-antigen-presenting cells. J. Invest. Dermatol., 94: 485–491.
Ho VC, O Baadsgaard, JT Elder, et al., 1990a. Geno-typic analysis of T-cell clones derived from cutaneous T-cell lymphoma lesions demonstrates selective growth of tumor infiltrating lymphocytes. J. Invest. Dermatol., 95: 4–8.
Ho VC, ER Hansen, JT Elder, et al., 1990b. T cell receptor beta-chain gene rearrangement without gamma-chain gene rearrangement in cutaneous T cell lymphoma: An unusual finding. Clin. Immunol. Immunopathol., 54: 354–360.
Koller U, V Groh, O Majdic, H Stockinger and W Knapp, 1987. Subclustering of CD1 antibodies on the basis of their reaction pattern with different types of dendritic cells. In: AJ McMichael, PCL Beverley, W Gilks et al., Eds., Leucocyte Typing m. White Cell Differentiation Antigens, Oxford, Oxford University Press, pp. 85–86.
Lisby S, O Baadsgaard, KD Cooper, K Thomsen and GRL Wantzin, 1988. Expression of 0KM5 antigen on epidermal cells in mycosis fungoides plaque stage. J. Invest. Dermatol., 90: 716–719.
Lisby S, O Baadsgaard, KD Cooper, et al., 1990. Phenotype, ultrastructure, and function of CD1+DR+ epidermal cells that express CD36 (0KM5) in cutaneous T cell lymphoma. Scand. J. Immunol., 32: 111–119.
Murphy GF, BR Bronstein, RW Knowles and AK Bhan, 1985. Ultrastructural documentation of M241 glycoprotein on dendritic and endothelial cells in normal human skin. Lab. Invest., 52: 264–269.
Nickoloff BJ, CEM Griffiths, O Baadsgaard, JJ Voorhees, CA Hanson and KD Cooper, 1989. Markedly diminished epidermal keratinocyte expression of intercellular adhesion molecule-1 (ICAM-1) in Sézary syndrome. JAMA, 261: 2217–2221.
Steinman RM and MC Nussenzweig, 1980. Dendritic cells: features and functions. Immunol. Rev., 53: 127–147.
Taylor RS, O Baadsgaard, C Hammerberg and KD Cooper, 1991. Hyperstimulatory CDla+CDlb+CD36+ Langerhans cells are responsible for increased autologous T lymphocyte reactivity to lesionai epidermal cells of patients with atopic dermatitis. J. Immunol., 147: 3794–3802.
Tjernlund UM, 1978. Epidermal expression of HLA-DR antigens in mycosis fungoides. Arch. Dermatol. Res., 261: 81–86.
Vonderheid E, 1989. Diagnostic Methods for Cutaneous T-Cell Lymphoma. In: SA Muller, Ed., Parapsoriasis, Rochester, Mayo Foundation, p. 83–94.
Vonderheid EC, DW Tarn, WC Johnson, EJ Van Scott and PE Wallner, 1981. Prognostic significance of cytomorphology in the cutaneous T-cell lymphomas. Cancer, 47: 119–125.
Waldmann TA, MM Davis, KF Bongiovanni and SKJ Korsmeyer, 1985. Rearrangements of genes for the antigen receptor on T cells as markers of lineage and clonality in human lymphoid neoplasms. N. Engl. J. Med., 313: 776–783.
Weiss JS, WD James and KD Cooper, 1988. Melanophages in inflammatory skin disease demonstrate the surface phenotype of OKM5+ antigen-presenting cells and activated macrophages. J. Am. Acad. Dermatol., 19: 633–641.
Weiss LM, E Hu, GS Wood, et al., 1985. Clonal re-arrangements of T-cell receptor genes in mycosis fungoides and dermatopathic lymphadenopathy. N. Engl. J. Med., 313: 539–544.
Weiss LM, GS Wood, E Hu, EA Abel, RT Hoppe and J Sklar, 1989. Detection of clonal T-cell receptor gene rearrangements in the peripheral blood of patients with mycosis fungoides/Sézary syndrome. J. Invest. Dermatol., 92: 601–604.
Wood GS, DG Deneau, RA Miller, R Levy, RT Hoppe, and RA Warnke, 1982. Subtypes of cutaneous T-cell lymphoma defined by expression of leu-1 and Ia. Blood, 59: 876–882.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1994 Springer Science+Business Media New York
About this chapter
Cite this chapter
Cooper, K.D. et al. (1994). Activation of Reactive Versus Malignant T Cells in Cutaneous T Cell Lymphoma: Role of Abnormal Antigen Presenting Cells and T Cell Activating Molecules. In: Lambert, W.C., Giannotti, B., van Vloten, W.A. (eds) Basic Mechanisms of Physiologic and Aberrant Lymphoproliferation in the Skin. NATO ASI Series, vol 265. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-1861-7_3
Download citation
DOI: https://doi.org/10.1007/978-1-4615-1861-7_3
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4613-5756-8
Online ISBN: 978-1-4615-1861-7
eBook Packages: Springer Book Archive