title: Follicular lymphoma B cells induce the conversion of conventional CD4+ T cells to T-regulatory cells.
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.
authors.affiliation: Department of Medicine, Divisions of Oncology, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Weiyun Z
authors.initials: WZ
authors.lastname: Ai
authors.forename: Jing-Zhou
authors.initials: JZ
authors.lastname: Hou
authors.forename: Robert
authors.initials: R
authors.lastname: Zeiser
authors.forename: Debra
authors.initials: D
authors.lastname: Czerwinski
authors.forename: Robert S
authors.initials: RS
authors.lastname: Negrin
authors.forename: Ronald
authors.initials: R
authors.lastname: Levy
mesh_terms: D001402:B-Lymphocytes / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018925:Chemokines / Q000378:metabolism; D018920:Coculture Techniques; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D007107:Immune System; D008198:Lymph Nodes / Q000473:pathology; D008224:Lymphoma, Follicular / Q000378:metabolism*; D008954:Models, Biological; D010641:Phenotype; D013601:T-Lymphocytes / Q000378:metabolism*; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism*
chemical_list: D018925:Chemokines; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors