Possible origin of adult T-cell leukemia/lymphoma cells from human T lymphotropic virus type-1-infected regulatory T cells.
Adult T-cell leukemia/lymphoma (ATLL) is a lymphoproliferative disorder caused by human T lymphotropic virus type 1 (HTLV-I). Although ATLL cells display an activated helper/inducer T-cell phenotype, CD4+ and CD25+, they are known to exhibit strong immunosuppressive activity. As regulatory T cells (Treg cells) express CD4+ and CD25+ molecules and possess potent immune response suppressive activity, we investigated a possible link between ATLL cells and Treg cells. In primary ATLL cells, the expression levels of the Treg cell marker molecules Foxp3 and glucocorticoid-induced tumor necrosis factor receptor family related protein (GITR) were significantly higher than in those from healthy adults. Furthermore, ATLL cells are unresponsive in vitro to concanavalin A stimulation and suppress the proliferation of normal T cells. GITR mRNA expression was induced by the HTLV-I transactivator Tax, and GITR promoter analyses revealed that this induction depends on the kappaB site from -431 bp to -444 bp upstream of the putative transcription site. Taken together, ATLL cells may originate from HTLV-I-infected Treg cells, and GITR seems to be involved in the progression to ATLL.
Kohno
Tomoko
T
Division of Cytokine Signaling, Department of Molecular Microbiology and Immunology, Nagasaki University, Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan.
Yamada
Yasuaki
Y
Akamatsu
Norihiko
N
Kamihira
Simeru
S
Imaizumi
Yoshitaka
Y
Tomonaga
Masao
M
Matsuyama
Toshifumi
T
D000328:Adult; D002455:Cell Division; D045744:Cell Line, Tumor; D003208:Concanavalin A; D004268:DNA-Binding Proteins / Q000235:genetics; D051858:Forkhead Transcription Factors; D015972:Gene Expression Regulation, Neoplastic; D015967:Gene Expression Regulation, Viral; D016356:Gene Products, tax / Q000378:metabolism; D053450:Glucocorticoid-Induced TNFR-Related Protein; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D008213:Lymphocyte Activation; D017475:Receptors, Nerve Growth Factor / Q000235:genetics; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology*
D004268:DNA-Binding Proteins; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D016356:Gene Products, tax; D053450:Glucocorticoid-Induced TNFR-Related Protein; D017475:Receptors, Nerve Growth Factor; D018124:Receptors, Tumor Necrosis Factor; C491405:TNFRSF18 protein, human; D003208:Concanavalin A