Regulatory T-cell therapy for transplantation:  how many cells do we need?
OBJECTIVE
As regulatory T-cell (Treg) therapy begins to enter the clinic and more clinical trials of Treg therapy are being actively planned for solid organ transplantations, a thorough quantitative assessment of therapeutic dosing is essential for the design of an effective Treg-therapy trial in the solid organ transplant setting.


RESULTS
Considering the requirement for a high percentage of Tregs to control transplant rejection in mouse models of transplantation and the total cellularity of the human T-cell compartment, we estimate that it would take billions of Tregs, preferably alloantigen-reactive Tregs, to effectively control transplant rejection in humans. Donor dendritic cells and B cells can be used to selectively expand donor alloantigen-reactive Tregs. Recent improvements in manufacturing alloantigen-reactive Tregs demonstrate that billions of alloantigen-reactive T cells can be manufactured in short-term cultures.


CONCLUSIONS
It is feasible to grow human alloantigen-reactive Tregs up to billions, an optimal number to achieve therapeutic efficacy. Better understanding of Treg lineage commitment and further technological investments are needed to ease the implementation and ensure consistency in Treg manufacturing.
Department of Surgery, University of California, San Francisco, California 94143-0780, USA. Qizhi.Tang@ucsfmedctr.org
Qizhi
Q
Tang
Karim
K
Lee
D000818:Animals; D064987:Cell- and Tissue-Based Therapy; D006084:Graft Rejection / Q000276:immunology* / Q000517:prevention & control; D006801:Humans; D018655:Lymphocyte Count; D016377:Organ Transplantation; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000637:transplantation