Regulatory T cell-like activity of Foxp3+ adult T cell leukemia cells.
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.
Chen
Shuming
S
Department of Microbiology and Immunology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan.
Ishii
Naoto
N
Ine
Shouji
S
Ikeda
Syuichi
S
Fujimura
Taku
T
Ndhlovu
Lishomwa C
LC
Soroosh
Pejman
P
Tada
Kohtaro
K
Harigae
Hideo
H
Kameoka
Junichi
J
Kasai
Noriyuki
N
Sasaki
Takeshi
T
Sugamura
Kazuo
K
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*
C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D016356:Gene Products, tax