Treg in GVHD Prophylaxis: Unique Transcription Factor Regulation of Foxp3 Expression in Itreg Derived from Human Umbilical Cord Blood (UCB) Vs Adult (AB) Naive CD4 T Cells

Early clinical experience identifies third party allogeneic natural T regulatory cells (nTreg) to be safe and effective in acute GVHD (aGVHD) prophylaxis (CG Brunstein et al. 2016). However the low proliferative potential of nTreg remains a challenge to broader clinical application. Inducible Treg (iTreg) can reestablish tolerance in settings where Tregs are decreased or defective. However instability of expression of Transcription factor Fork head box P3 (Foxp3), essential for CD4+ iTreg induction and function, also poses a significant barrier to successful clinical application. Further understanding of Foxp3 transcription factor partners and their function is emerging. Foxp3 is known to regulate Treg function through cooperation with Nuclear Factor of Activated T-Cells (NFAT1). More recently, broad complex-Tramtrack-Bric-a-brac domain (BTB) and Cap9n9collar (CNC) homology 1, basic leucine zipper transcription factor 2 (BACH2) has been shown to repress effector programs to stabilize Treg-mediated immune homeostasis in murine KO studies (Roychoudhuri R. 2013). However, little is known in normal human CD4 T cells what role, if any, BACH2 may play in Foxp3+ regulation. Previous work by this group identified higher BACH2 expression in UCB vs. AB CD4+ T cells, and further that BACH2 regulates expression of IL-2 in UCB CD4+ T-cells lacking normal expression of NFAT1 protein (M. Lesniewski et al. 2008). In our current studies, we compared BACH2 function in Foxp3+ iTreg derived from UCB vs. AB naive CD4+CD45RA+ cells. We observe that: i.) naive UCB CD4+ T cells highly express BACH2, 21-fold higher compared to AB CD4+ T cells (including protein and mRNA expression (n=6; p Disclosures No relevant conflicts of interest to declare.