title: Regulatory T cell-like activity of Foxp3+ adult T cell leukemia cells.
abstract: Adult T cell leukemia (ATL) is an aggressive neoplastic disease, in which a quarter of the patients develop opportunistic infections due to cellular immunodeficiency. However, the underlying mechanism responsible for the immunosuppression has remained unclear. Recent studies have demonstrated that the leukemia cells from a subset of patients with ATL express Foxp3, a specific marker for CD25+CD4+ regulatory T (Treg) cells, which regulate the immune response by suppressing CD4+ T cell functions. However, whether there is a functional resemblance between ATL cells that have Foxp3 expression and Treg cells is still unknown. In this report, we confirmed the high expression of Foxp3 in leukemia cells from 5 of 12 ATL patients and demonstrated that ATL cells from 3 patients suppressed the proliferation of CD4+ T cells. Similarly, one of six HTLV-I-infected cell lines showed both high Foxp3 expression and suppressive activity. Like Treg cells, the suppression induced by the ATL cells from two patients and the HTLV-infected cell line appeared to be mediated by a cell-cell contact-dependent mechanism. Nevertheless, among the ATL cells that strongly expressed Foxp3, those from two of the five patients showed no apparent suppressive activity. Furthermore, retroviral transfection of Foxp3 did not confer any suppressive function on low Foxp3-expressing HTLV-I-infected cell lines. These results indicate that Foxp3 may be essential but is not sufficient for the Treg-cell-like suppressive activity of ATL cells and HTLV-I-infected cell lines.
authors.affiliation: Department of Microbiology and Immunology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan.
authors.forename: Shuming
authors.initials: S
authors.lastname: Chen
authors.forename: Naoto
authors.initials: N
authors.lastname: Ishii
authors.forename: Shouji
authors.initials: S
authors.lastname: Ine
authors.forename: Syuichi
authors.initials: S
authors.lastname: Ikeda
authors.forename: Taku
authors.initials: T
authors.lastname: Fujimura
authors.forename: Lishomwa C
authors.initials: LC
authors.lastname: Ndhlovu
authors.forename: Pejman
authors.initials: P
authors.lastname: Soroosh
authors.forename: Kohtaro
authors.initials: K
authors.lastname: Tada
authors.forename: Hideo
authors.initials: H
authors.lastname: Harigae
authors.forename: Junichi
authors.initials: J
authors.lastname: Kameoka
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Kasai
authors.forename: Takeshi
authors.initials: T
authors.lastname: Sasaki
authors.forename: Kazuo
authors.initials: K
authors.lastname: Sugamura
mesh_terms: D000328:Adult; D000368:Aged; D045744:Cell Line, Tumor; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D016356:Gene Products, tax / Q000096:biosynthesis; D015368:Human T-lymphotropic virus 1 / Q000276:immunology; D006801:Humans; D016867:Immunocompromised Host; D015458:Leukemia, T-Cell / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D016356:Gene Products, tax