Session Time: 6:00pm-7:00pm
Presentation Time: 6:00pm-7:00pm
Location: Hall C & D
*Purpose: Conventional CD4+ T cells are key effectors of allograft rejection and novel therapies limiting their response may hold promise in the context of organ transplantation. The purpose of this project was to investigate the transcriptional programs differentially induced in alloreactive CD4+ T cells during transplant rejection versus tolerance
*Methods: We are using a mouse model of cardiac transplantation in which costimulation blockade with anti-CD154 and donor-specific transfusion induce donor-specific tolerance.
*Results: When compared with alloreactive CD4+ T cells in untreated mice that undergo acute rejection, alloreactive CD4+ T cells from tolerant mice acquire cell-intrinsic dysfunction and express a unique transcriptional profile that includes downregulation of special AT-rich sequence binding protein-1 (Satb1). Selective deficiency of Satb1 in CD4+ T cells results in prolonged cardiac and skin allograft survival without immunosuppression. Mechanistically, Satb1-deficient CD4+ T cells are enriched in inhibitory molecules PD1 and TIGIT upon TCR stimulation, while activation markers CD69 and GITR are down-modulated. Although Satb1-deficient CD4+ T cells retain proliferative capacity upon stimulation, they display increased susceptibility to T regulatory cell (Treg)-mediated suppression, which can be overcome by addition of exogenous IL-2.
*Conclusions: Thus, lack of Satb1 in conventional CD4+ T cells results in their increased suppression by Tregs and diminished anti-allograft immunity, suggesting Satb1 as a promising therapeutic target to improve transplant outcome in the clinic.
To cite this abstract in AMA style:Gupta PK, Miller ML, Chen L, Wang Y, Conejo-Garcia J, Chong A, Alegre M. Deficiency of the Transcription Factor Satb1 in T Cells Promotes Solid Organ Allograft Survival [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/deficiency-of-the-transcription-factor-satb1-in-t-cells-promotes-solid-organ-allograft-survival/. Accessed May 9, 2021.
« Back to 2019 American Transplant Congress