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 Blood, 1 October 2007, Vol. 110, No. 7, pp. 2537-2544.
Prepublished online as a Blood First Edition Paper on July 5, 2007; DOI 10.1182/blood-2007-03-082578.

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Submitted March 28, 2007
Accepted July 3, 2007

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, and Stephen M Ansell*

Division of Hematology & Internal Medicine, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, MN, United States

* Corresponding author; email: ansell.stephen{at}mayo.edu.

Foxp3 expression was initially thought to be restricted to the CD4+CD25+ regulatory T cell population. However, recent studies suggest that 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.


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