Session Time: 6:00pm-7:00pm
Presentation Time: 6:00pm-7:00pm
Location: Hall 4EF
Background: Perioperative ischemia reperfusion injury (IRI) is a consequence of solid organ allograft transplantation that primes the graft for future rejection.
Methods: We developed an in vitro model of IRI in which IFNy-pretreated human umbilical vein endothelial cells (EC) are cultured with human serum in gelatin veronal buffer (GVB) under hypoxic conditions to induce complement activation.
Results: IRI-like treatment of EC causes non-lytic IgM dependent terminal complement deposition and upregulation of ICOS-L and PD-L2, which were detected in in vitro and in vivo, replicating findings from human renal biopsies with confirmed complement deposition. Because ICOS-L and PD-L2 are cognate ligands of surface markers for both follicular T helper cells (Tfh) and peripheral T helper cells (Tph), we compared how these T cell subsets respond to the EC. In co-culture, IRI-like treated ECs induced selective expansion of allogeneic Tph compared to Tfh cells (p=0.0078). Analysis of Tph and Tfh cells from these co-cultures by Time of Flight Mass Cytometry (CyTOF) demonstrated increased expression of activation markers (HLA-DR, IL-2, IL-4, IL-21, and BCL-6) in Tph compared with Tfh. Activated Tph cells were significantly more effective than Tfh at mediating plasmablast production of DSA from autologous peripheral blood B cells (p=0.0003).
Conclusions: We developed a novel human model for IRI-like treatment of human EC in vitro that activates complement. Such EC selectively expand and activate allogeneic Tph over Tfh, and the activated Tph support DSA production by plasmablasts. These data suggest a possible mechanistic link between IRI and future rejection.
CITATION INFORMATION: Fu W., Yoo P., Pober J., Jane-wit D. Peripheral but Not Follicular T Helper Cells Are Activated by Allogeneic Human Endothelial Cells under IRI-Like Conditions and Promote Donor Specific Antibody Am J Transplant. 2017;17 (suppl 3).
To cite this abstract in AMA style:Fu W, Yoo P, Pober J, Jane-wit D. Peripheral but Not Follicular T Helper Cells Are Activated by Allogeneic Human Endothelial Cells under IRI-Like Conditions and Promote Donor Specific Antibody [abstract]. https://atcmeetingabstracts.com/abstract/peripheral-but-not-follicular-t-helper-cells-are-activated-by-allogeneic-human-endothelial-cells-under-iri-like-conditions-and-promote-donor-specific-antibody/. Accessed July 23, 2021.
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