Chronic lymphocytic leukemia and regulatory B cells share IL-10 competence and immunosuppressive function

D. J. Dilillo, J. B. Weinberg, A. Yoshizaki, M. Horikawa, J. M. Bryant, Y. Iwata, T. Matsushita, K. M. Matta, Y. Chen, G. M. Venturi, G. Russo, J. P. Gockerman, J. O. Moore, L. F. Diehl, A. D. Volkheimer, D. R. Friedman, M. C. Lanasa, R. P. Hall, T. F. Tedder

研究成果: Article査読

110 被引用数 (Scopus)

抄録

Chronic lymphocytic leukemia (CLL) can be immunosuppressive in humans and mice, and CLL cells share multiple phenotypic markers with regulatory B cells that are competent to produce interleukin (IL)-10 (B10 cells). To identify functional links between CLL cells and regulatory B10 cells, the phenotypes and abilities of leukemia cells from 93 patients with overt CLL to express IL-10 were assessed. CD5 + CLL cells purified from 90% of the patients were IL-10-competent and secreted IL-10 following appropriate ex vivo stimulation. Serum IL-10 levels were also significantly elevated in CLL patients. IL-10-competent cell frequencies were higher among CLLs with IgV H mutations, and correlated positively with TCL1 expression. In the TCL1-transgenic (TCL1-Tg) mouse model of CLL, IL-10-competent B cells with the cell surface phenotype of B10 cells expanded significantly with age, preceding the development of overt, CLL-like leukemia. Malignant CLL cells in TCL1-Tg mice also shared immunoregulatory functions with mouse and human B10 cells. Serum IL-10 levels varied in TCL1-Tg mice, but in vivo low-dose lipopolysaccharide treatment induced IL-10 expression in CLL cells and high levels of serum IL-10. Thus, malignant IL-10-competent CLL cells exhibit regulatory functions comparable to normal B10 cells that may contribute to the immunosuppression observed in patients and TCL1-Tg mice.

本文言語English
ページ(範囲)170-182
ページ数13
ジャーナルLeukemia
27
1
DOI
出版ステータスPublished - 01-2013
外部発表はい

All Science Journal Classification (ASJC) codes

  • 血液学
  • 腫瘍学
  • 癌研究

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