title: Cutaneous T cell lymphoma expresses immunosuppressive CD80 (B7-1) cell surface protein in a STAT5-dependent manner.
abstract: In this article, we report that cutaneous T cell lymphoma (CTCL) cells and tissues ubiquitously express the immunosuppressive cell surface protein CD80 (B7-1). CD80 expression in CTCL cells is strictly dependent on the expression of both members of the STAT5 family, STAT5a and STAT5b, as well as their joint ability to transcriptionally activate the CD80 gene. In IL-2-dependent CTCL cells, CD80 expression is induced by the cytokine in a Jak1/3- and STAT5a/b-dependent manner, whereas in the CTCL cells with constitutive STAT5 activation, CD80 expression is also STAT5a/b dependent but is independent of Jak activity. Although depletion of CD80 expression does not affect the proliferation rate and viability of CTCL cells, induced expression of the cell-inhibitory receptor of CD80, CD152 (CTLA-4), impairs growth of the cells. Coculture of CTCL cells with normal T lymphocytes consisting of both CD4(+) and CD8(+) populations or the CD4(+) subset alone, transfected with CD152 mRNA, inhibits proliferation of normal T cells in a CD152- and CD80-dependent manner. These data identify a new mechanism of immune evasion in CTCL and suggest that the CD80-CD152 axis may become a therapeutic target in this type of lymphoma.
authors: Department of Pathology and Laboratory Medicine, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA 19104;
authors: Qian
authors: Q
authors: Zhang
authors: Hong Yi
authors: HY
authors: Wang
authors: Fang
authors: F
authors: Wei
authors: Xiaobin
authors: X
authors: Liu
authors: Jennifer C
authors: JC
authors: Paterson
authors: Darshan
authors: D
authors: Roy
authors: Daniela
authors: D
authors: Mihova
authors: Anders
authors: A
authors: Woetmann
authors: Andrzej
authors: A
authors: Ptasznik
authors: Niels
authors: N
authors: Odum
authors: Stephen J
authors: SJ
authors: Schuster
authors: Teresa
authors: T
authors: Marafioti
authors: James L
authors: JL
authors: Riley
authors: Mariusz A
authors: MA
authors: Wasik
mesh_terms: D000328:Adult; D018122:B7-1 Antigen / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015153:Blotting, Western; D060908:CTLA-4 Antigen / Q000276:immunology / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002478:Cells, Cultured; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D007376:Interleukin-2 / Q000494:pharmacology; D053613:Janus Kinase 1 / Q000276:immunology / Q000378:metabolism; D053616:Janus Kinase 3 / Q000276:immunology / Q000378:metabolism; D016410:Lymphoma, T-Cell, Cutaneous / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D018448:Models, Immunological; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050799:STAT5 Transcription Factor / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
chemical_list: D018122:B7-1 Antigen; D060908:CTLA-4 Antigen; D007376:Interleukin-2; D050799:STAT5 Transcription Factor; C494092:STAT5A protein, human; C494095:STAT5B protein, human; D025521:Tumor Suppressor Proteins; C507933:JAK3 protein, human; D053613:Janus Kinase 1; D053616:Janus Kinase 3