Human regulatory T cells suppress proliferation of B lymphoma cells

Abstract

Activated regulatory T cells (Tregs) suppress proliferation and differentiation of normal B cells. In our study, allogeneic polyclonal CD4 ⁺ CD25 ⁺ Tregs and CD4 ⁺ CD25 ⁺ CD127^loTregs expanded in vitro in the presence of rapamycin and low dose IL-2 suppressed proliferation of 11 out of 12 established lymphoma B-cell lines. The effect of expanded CD4 ⁺ CD25 ⁺ Tregs on survival of freshly isolated lymphoma B cells maintained in culture with soluble multimeric CD40L and IL-4 was variable across lymphoma entities. The survival of freshly isolated follicular lymphoma cells usually decreased in cocultures with CD4 ⁺ CD25 ⁺ Tregs. Treg effect on chronic lymphocytic leukemia/small lymphocytic lymphoma cells ranged from suppression to help in individual patients. CD4 ⁺ CD25 ⁺ Tregs or CD4 ⁺ CD25 ⁺ CD127^loTregs expanded ex vivo with rapamycin could be used to suppress regrowth of residual lymphoma after autologous hematopoietic cell transplantation (HCT), and to counteract both graft-versus-host disease and lymphoma re-growth after allogeneic HCT in select patients with lymphoma susceptible to the regulation by Tregs.

Keywords:

• B-cell lymphoma
• dendritic cells
• immune regulation
• regulatory T cells
• tumor immunology

Acknowledgements

This work was supported by a grant from National Science Center, Poland (N N402 454739) for S. M.

 Prof. Walewski reports grants from National Science Center, Poland, during the conduct of the study; grants, personal fees, and other from Roche, personal fees, and other from Takeda, grants, and personal fees from Mundipharma, grants, personal fees, and other from Celgene, personal fees from Teva, personal fees, and other from Gilead, personal fees, and other from Sanofi, personal fees from Janssen-Cilag, personal fees from Boehringer Ingelheim, personal fees from Karyopharm, personal fees from Ariad, grants from GSK/Novartis, other from Seattle Genetics, outside the submitted work; Dr. Paszkiewicz-Kozik reports grants from National Science Center, Poland, during the conduct of the study; personal fees, and other from Roche, personal fees from Sandoz, outside the submitted work; M.Sc. Biernacka, M.Sc. Borycka, M.Sc. Grygorowicz, M.Sc. Nowak, Dr. Bujko, Prof Markowicz reports grants and personal fees from National Science Center, Poland, during the conduct of the study; Dr. Rymkiewicz and Dr. Bystydzienski reports grants from National Science Center, Poland, during the conduct of the study.

Potential conflict of interest

Disclosure forms provided by the authors are available with the full text of this article at http://dx.doi.org/10.3109/10428194.2015.1121260