CD70+ non-Hodgkin lymphoma B cells induce Foxp3 expression and regulatory function in intratumoral CD4+CD25- T cells

Zhi Zhang Yang, Anne J Novak, Steven C. Ziesmer, Thomas Elmer Witzig, Stephen Maxted Ansell

Research output: Contribution to journalArticle

126 Citations (Scopus)

Abstract

Foxp3 expression was initially thought to be restricted to the CD4 +CD25+ regulatory T-cell population. However, recent studies suggest that forkhead box P3 (Foxp3) is expressed in CD4 +CD25- T cells in aged mice. In the present study in B-cell non-Hodgkin lymphoma (NHL), we found that a subset of intratumoral but not peripheral blood CD4+CD25- T cells, comprising about 15% of intratumoral CD4+ T cells, express Foxp3 and are capable of suppressing the proliferation of autologous infiltrating CD8+ T cells. In vitro activation with OKT3/anti-CD28 antibody (Ab) or dendritic cells (DCs) induced Foxp3 expression in a subset of these CD4+CD25 -Foxp3- T cells. We found that the presence of lymphoma B cells during activation augmented activation-induced Foxp3 expression in CD4+CD25- T cells. We also found that CD70+ lymphoma B cells significantly contributed to the activation-induced Foxp3 expression in intratumoral CD4+CD25- T cells. Furthermore, the blockade of CD27-CD70 interaction by anti-CD70 Ab abrogated lymphoma B-cell-mediated induction of Foxp3 expression in intratumoral CD4 +CD25- T cells. Taken together, these studies reveal a novel role for NHL B cells in the development of intratumoral regulatory T cells.

Original languageEnglish (US)
Pages (from-to)2537-2544
Number of pages8
JournalBlood
Volume110
Issue number7
DOIs
StatePublished - Oct 1 2007

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T-cells
Non-Hodgkin's Lymphoma
B-Lymphocytes
Cells
T-Lymphocytes
B-Cell Lymphoma
Chemical activation
Regulatory T-Lymphocytes
Anti-Idiotypic Antibodies
Muromonab-CD3
Dendritic Cells
Antibodies
Blood

ASJC Scopus subject areas

  • Hematology

Cite this

CD70+ non-Hodgkin lymphoma B cells induce Foxp3 expression and regulatory function in intratumoral CD4+CD25- T cells. / Yang, Zhi Zhang; Novak, Anne J; Ziesmer, Steven C.; Witzig, Thomas Elmer; Ansell, Stephen Maxted.

In: Blood, Vol. 110, No. 7, 01.10.2007, p. 2537-2544.

Research output: Contribution to journalArticle

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