Follicular lymphoma B cells induce the conversion of conventional CD4+ T cells to T-regulatory cells

Int J Cancer. 2009 Jan 1;124(1):239-44. doi: 10.1002/ijc.23881.

Abstract

There has been accumulating evidence that CD4(+)CD25(+) FoxP3 expressing regulatory T cells (Treg) are highly concentrated in tumors, thereby fostering an immune-privileged microenvironment. Some studies have shown that T-cell receptor (TCR) stimulation can convert conventional T cells into Treg. Follicular lymphoma (FL) B cells can enhance this Treg conversion. We investigated whether FL tumor B cells, as opposed to normal B cells, are unique in their ability to convert effector T cells into Treg. We found that tumor B cells alone, without artificial TCR stimulation, could induce conventional T cells to express FoxP3 and to acquire regulatory function. In contrast to their malignant counterpart, normal B cells did not induce Treg conversion. Treg conversion was independent of the T cell background, as T cells isolated from FL or normal peripheral blood were equally susceptible to being converted by tumor B cells. Our study provides evidence for a tumor-specific mechanism by which FL tumor cells promote immune escape through the induction of Treg.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • B-Lymphocytes / metabolism*
  • CD4-Positive T-Lymphocytes / metabolism*
  • Cell Line, Tumor
  • Cell Proliferation
  • Chemokines / metabolism
  • Coculture Techniques
  • Forkhead Transcription Factors / metabolism
  • Humans
  • Immune System
  • Lymph Nodes / pathology
  • Lymphoma, Follicular / metabolism*
  • Models, Biological
  • Phenotype
  • T-Lymphocytes / metabolism*
  • T-Lymphocytes, Regulatory / metabolism*

Substances

  • Chemokines
  • FOXP3 protein, human
  • Forkhead Transcription Factors