Journal
FRONTIERS IN IMMUNOLOGY
Volume 12, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2021.679675
Keywords
immune regulation; regulatory T cell; Treg therapy; dendritic cells; B cells; human; transplantation; transplant tolerance
Categories
Funding
- NIAID/CTOT (Clinical Trials in Organ Transplant) grant [A130726, 1U01AI110658, R01 AI 118777, U19 AI 131453, U01 AI 36779, T32 AI 74490]
- Burroughs Wellcome Fund Collaborative Research Travel grant
- UC Davis Immune Monitoring Shared Resource [5P30CA093373]
- UCSF Parnassus Flow Core [RRID:SCR_018206]
- DRC Center Grant NIH [P30 DK063720]
- NIH [1S10OD018040-01]
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In this study comparing arTregs expanded ex vivo using different types of antigen-presenting cells, it was found that sDCs stimulated Tregs to expand in much larger numbers. Additionally, sDC-generated arTregs expressed higher levels of CD80, CD86, and T cell-attracting chemokines, indicating their superior expansion-inducing capacity.
Alloreactive regulatory T cells (arTregs) are more potent than polyclonal Tregs at suppressing immune responses to transplant antigens. Human arTregs can be expanded with allogeneic CD40L-stimulated B cells (sBcs) or stimulated-matured monocyte-derived dendritic cells (sDCs). Here, we compared the expansion efficiency and properties of arTregs stimulated ex vivo using these two types of antigen-presenting cells. Compared to sBcs, sDCs stimulated Tregs to expand two times more in number. The superior expansion-inducing capacity of sDCs correlated with their higher expression of CD80, CD86, and T cell-attracting chemokines. sBc- and sDC-arTregs expressed comparable levels of FOXP3, HELIOS, CD25, CD27, and CD62L, demethylated FOXP3 enhancer and in vitro suppressive function. sBc- and sDCs-arTregs had similar gene expression profiles that were distinct from primary Tregs. sBc- and sDC-arTregs exhibited similar low frequencies of IFN-gamma, IL-4, and IL-17A-producing cells, and the cytokine-producing arTregs expressed high levels of FOXP3. Almost all sBc- and sDC-arTregs expressed CXCR3, which may enable them traffic to inflammatory sites. Thus, sDCs-arTregs that expand more readily, are phenotypically similar to sBc-arTregs, supporting sDCs as a viable alternative for arTreg production for clinical evaluation.
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