Complement‐activated human endothelial cells stimulate increased polyfunctionality in alloreactive T cells. Issue 5 (1st February 2021)

• Record Type: Journal Article
• Authors: Xie, Catherine B.; Zhou, Jing; Mackay, Sean; Pober, Jordan S.
• Is Part Of: American journal of transplantation. Volume 21:Issue 5(2021)
• Page Start: 1902
• Page End: 1909
• Publication Date: 2021-02-01
• Subjects: alloantibody -- basic (laboratory) research/science -- complement biology -- immunobiology -- molecular biology -- organ transplantation in general -- proteomics -- T cell biology -- translational research/science -- vascular biology; Transplantation of organs, tissues, etc -- Periodicals; 617.95
• DOI: 10.1111/ajt.16485
• Languages: English
• ISSNs: 1600-6135

Abstract

Abstract : Antibody‐mediated deposition of complement membrane attack complexes (MACs) on IFN‐γ‐primed human endothelial cells (ECs) triggers autocrine/paracrine IL‐1β‐mediated EC activation and IL‐15 transpresentation to alloreactive effector memory T cells (TEM ), changes that enable ECs to increase T cell proliferation and cytokine release. Here, we report the use of single‐cell microchip 32‐plex proteomics to more deeply assess the functionality of the activated T cells and dependence upon EC‐derived signals. Compared to control ECs, MAC‐activated human ECs increase both the frequency and degree of polyfunctionality among both CD4 + and CD8 + ‐proliferated TEM, assessed as secreted proteins. IFN‐γ and TNF‐α remain the predominant cytokines made by alloreactive TEM, but a few CD4 + TEM also made IL‐4 while more CD8 + TEM made perforin and granzyme B. Increased polyfunctionality was attenuated by treatment of the MAC‐activated ECs with anti‐IL‐15 blocking antibody more effectively than IL‐1 receptor blockade. The increased polyfunctionality of T cells resulting from interactions with MAC‐activated ECs may further link binding of donor‐specific antibody to T cell–mediated allograft pathologies. Abstract : Analysis of the single cell protein secretome of human CD4+ and CD8+ effector memory T cells activated by coculture with allogeneic endothelial cells reveals that IL‐15, expressed on endothelium in response to alloantibody and complement‐mediated activation, increases both polyfunctionality and intensity of the T cell response, further linking humoral and cellular alloimmunity through endothelial cell interactions.