Follicular lymphoma B cells induce the conversion of conventional CD4+ T cells to T-regulatory cells.
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.
Ai
Weiyun Z
WZ
Department of Medicine, Divisions of Oncology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Hou
Jing-Zhou
JZ
Zeiser
Robert
R
Czerwinski
Debra
D
Negrin
Robert S
RS
Levy
Ronald
R
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*
D018925:Chemokines; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors