Delineation of immunoregulatory properties of adult T-cell leukemia cells.
We characterized leukemic cells from 20 adult T-cell leukemia (ATL) cases and 7 ATL-derived cell lines in terms of Foxp3 messenger RNA (mRNA) expression, cytokine production, cell surface markers associated with regulatory T-cells (Treg), and in vitro immunoregulatory activity and compared the results with those of cells from 3 T-cell-type chronic lymphocytic leukemia (T-CLL) patients and normal CD4+ T-cells. Real-time polymerase chain reaction analysis showed that cells from 10 ATL cases, 1 T-CLL case, and 1 ATL cell line had higher Foxp3 mRNA levels than CD4+ T-cells. In 5 ATL cases, Foxp3 levels were comparable to those of CD4+CD25+ T-cells. Flow cytometric analysis revealed that CTLA-4 expression correlated with Foxp3 mRNA level in ATL cells. The cells of all ATL cases examined produced no interleukin 2 or interferon gamma after iono-mycin and phorbolmyristate acetate stimulation. Cases with low Foxp3 expression (Foxp3-low) tended to express higher levels of transforming growth factor beta mRNA, but this trend was not statistically significant. An in vitro inhibition assay showed that the proliferation of normal CD4+CD25- T-cells stimulated with anti-CD3 monoclonal antibody and autologous dendritic cells was significantly suppressed by coculture with Foxp3-high ATL cells. These results indicate that Foxp3 expression is variable in ATL cases and that Foxp3-high ATL cells, which resemble Treg phenotypically as well as functionally, may be involved in immune suppression in ATL.
Matsubar
Yasushi
Y
Department of Hematology and Oncology, Graduate School of Medicine, Kyoto, Japan.
Hori
Toshiyuki
T
Morita
Rimpei
R
Sakaguchi
Shimon
S
Uchiyama
Takashi
T
D000368:Aged; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D005260:Female; D015973:Gene Expression Regulation, Leukemic / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance / Q000235:genetics; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000235:genetics / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D050378:T-Lymphocytes, Regulatory / Q000276:immunology