Cutaneous T cell lymphoma expresses immunosuppressive CD80 (B7-1) cell surface protein in a STAT5-dependent manner

TY - JOUR

T1 - Cutaneous T cell lymphoma expresses immunosuppressive CD80 (B7-1) cell surface protein in a STAT5-dependent manner

AU - Zhang, Qian

AU - Wang, Hong Yi

AU - Wei, Fang

AU - Liu, Xiaobin

AU - Paterson, Jennifer C

AU - Roy, Darshan

AU - Mihova, Daniela

AU - Andersen, Anders Woetmann

AU - Ptasznik, Andrzej

AU - Ødum, Niels

AU - Schuster, Stephen J

AU - Marafioti, Teresa

AU - Riley, James L

AU - Wasik, Mariusz A

PY - 2014/3/15

Y1 - 2014/3/15

N2 - 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 cellinhibitory 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. The Journal of Immunology, 2014, 192: 2913-2919.

AB - 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 cellinhibitory 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. The Journal of Immunology, 2014, 192: 2913-2919.

KW - Adult

KW - Antigens, CD80

KW - Blotting, Western

KW - CTLA-4 Antigen

KW - Cell Line, Tumor

KW - Cell Proliferation

KW - Cells, Cultured

KW - Gene Expression Regulation, Neoplastic

KW - Humans

KW - Immunohistochemistry

KW - Interleukin-2

KW - Janus Kinase 1

KW - Janus Kinase 3

KW - Lymphoma, T-Cell, Cutaneous

KW - Models, Immunological

KW - Oligonucleotide Array Sequence Analysis

KW - Reverse Transcriptase Polymerase Chain Reaction

KW - STAT5 Transcription Factor

KW - T-Lymphocytes

KW - Tumor Suppressor Proteins

U2 - 10.4049/jimmunol.1302951

DO - 10.4049/jimmunol.1302951

M3 - Journal article

C2 - 24523507

SN - 0022-1767

VL - 192

SP - 2913

EP - 2919

JO - Journal of Immunology

JF - Journal of Immunology

IS - 6

ER -