Cutaneous T cell lymphoma expresses immunosuppressive CD80 (B7-1) cell surface protein in a STAT5-dependent manner
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Cutaneous T cell lymphoma expresses immunosuppressive CD80 (B7-1) cell surface protein in a STAT5-dependent manner. / Zhang, Qian; Wang, Hong Yi; Wei, Fang; Liu, Xiaobin; Paterson, Jennifer C; Roy, Darshan; Mihova, Daniela; Andersen, Anders Woetmann; Ptasznik, Andrzej; Ødum, Niels; Schuster, Stephen J; Marafioti, Teresa; Riley, James L; Wasik, Mariusz A.
In: Journal of immunology (Baltimore, Md. : 1950), Vol. 192, No. 6, 15.03.2014, p. 2913-9.Research output: Contribution to journal › Journal article › Research › peer-review
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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 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.
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 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.
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
VL - 192
SP - 2913
EP - 2919
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 6
ER -
ID: 117551608