TY - JOUR
T1 - γc-Signaling Cytokines Induce a Regulatory T Cell Phenotype in Malignant CD4+ T Lymphocytes.
AU - Kasprzycka, Monika
AU - Zhang, Qian
AU - Witkiewicz, Agnieszka
AU - Marzec, Michal
AU - Potoczek, Magdalena
AU - Liu, Xiaobin
AU - Wang, Hong Yi
AU - Milone, Michael
AU - Basu, Samik
AU - Mauger, Joanne
AU - Choi, John K.
AU - Abrams, J. Todd
AU - Hou, J. Steven
AU - Rook, Alain H.
AU - Vonderheid, Eric
AU - Woetmann, Anders
AU - Odum, Niels
AU - Wasik, Mariusz A.
N1 - M1 - Copyright (C) 2018 American Chemical Society (ACS). All Rights Reserved.
CAPLUS AN 2008:936991(Journal)
PY - 2008
Y1 - 2008
N2 - In this study, we demonstrate that malignant mature CD4+ T lymphocytes derived from cutaneous T cell lymphomas (CTCL) variably display some aspects of the T regulatory phenotype. Whereas seven cell lines representing a spectrum of primary cutaneous T cell lymphoproliferative disorders expressed CD25 and TGF-β, the expression of FOXP3 and, to a lesser degree, IL-10 was restricted to two CTCL cell lines that are dependent on exogenous IL-2. IL-2, IL-15, and IL-21, all of which signals through receptors contg. the common γ chain, induced expression of IL-10 in the IL-2-dependent cell lines as well as primary leukemic CTCL cells. However, only IL-2 and IL-15, but not IL-21, induced expression of FOXP3. The IL-2-triggered induction of IL-10 and FOXP3 expression occurred by signaling through STAT3 and STAT5, resp. Immunohistochem. anal. of the CTCL tissues revealed that FOXP3-expressing cells were common among the CD7-neg. enlarged atypical and small lymphocytes at the early skin patch and plaque stages. Their frequency was profoundly diminished at the tumor stage and in the CTCL lymph node lesions with or without large cell transformation. These results indicate that the T regulatory cell features are induced in CTCL T cells by common γ chain signaling cytokines such as IL-2 and do not represent a fully predetd., constitutive phenotype independent of the local environmental stimuli to which these malignant mature CD4+ T cells become exposed. [on SciFinder(R)]
AB - In this study, we demonstrate that malignant mature CD4+ T lymphocytes derived from cutaneous T cell lymphomas (CTCL) variably display some aspects of the T regulatory phenotype. Whereas seven cell lines representing a spectrum of primary cutaneous T cell lymphoproliferative disorders expressed CD25 and TGF-β, the expression of FOXP3 and, to a lesser degree, IL-10 was restricted to two CTCL cell lines that are dependent on exogenous IL-2. IL-2, IL-15, and IL-21, all of which signals through receptors contg. the common γ chain, induced expression of IL-10 in the IL-2-dependent cell lines as well as primary leukemic CTCL cells. However, only IL-2 and IL-15, but not IL-21, induced expression of FOXP3. The IL-2-triggered induction of IL-10 and FOXP3 expression occurred by signaling through STAT3 and STAT5, resp. Immunohistochem. anal. of the CTCL tissues revealed that FOXP3-expressing cells were common among the CD7-neg. enlarged atypical and small lymphocytes at the early skin patch and plaque stages. Their frequency was profoundly diminished at the tumor stage and in the CTCL lymph node lesions with or without large cell transformation. These results indicate that the T regulatory cell features are induced in CTCL T cells by common γ chain signaling cytokines such as IL-2 and do not represent a fully predetd., constitutive phenotype independent of the local environmental stimuli to which these malignant mature CD4+ T cells become exposed. [on SciFinder(R)]
KW - cytokine regulatory T cell lymphoma
U2 - 10.4049/jimmunol.181.4.2506
DO - 10.4049/jimmunol.181.4.2506
M3 - Journal article
SN - 0022-1767
VL - 181
SP - 2506
EP - 2512
JO - Journal of Immunology
JF - Journal of Immunology
IS - 4
ER -