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 E. Witzig, Stephen M. Ansell

Research output: Contribution to journalArticlepeer-review

132 Scopus citations

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

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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