Session Time: 5:30pm-7:30pm
Presentation Time: 5:30pm-7:30pm
Location: Hall C & D
*Purpose: Interleukin-27 (IL-27), a member of IL-12 cytokine family, is involved in both pro- and anti-inflammatory immune responses. Previously we reported that B cell derived IL-27 facilitates reconstitution of CD8 T cells following lymphoablation. The goal of this study was to test the role of IL-27 in alloimmunity and allograft rejection.
*Methods: Full MHC-mismatched heart allografts were transplanted from BALB/c (H-2d) to naïve B6.WT or B6.IL-27R-/- mice (H-2b).
*Results: The absence of recipient IL-27R had no significant impact on graft survival (MST 7d, vs. 8d, for WT and IL27R-/-, respectively, n=6 mice/group). Furthermore, the frequencies of IFNγ-producing donor-reactive spleen T cells measured by ELISPOT were similar in both groups. However, donor specific antibody (DSA) generation was severely impaired in IL-27R-/- compared to WT recipients, with 65% and 75% reduction at d. 21 posttransplant for the levels of MHC class I- and class II-reactive DSA, respectively. To identify cell populations producing IL-27 following transplantation, we generated and used B6 IL-27 Tomato Red B6.IL-27TR reporter mice. We found that both before and after transplantation CD11b+CD11c– (66.7% TR+), CD11c+CD11b–CD8+ (93.8% TR+) and CD11c+CD11b–CD8– (71.6% TR+) cells were the main source of IL-27 at d. 12 posttransplant albeit 43.8% of CD138+ plasma cells also upregulated IL-27 at d. 7 posttransplant. We next tested the expression of IL-27R on various immune cells. Prior to transplantation, IL-27R was expressed on both naïve and memory CD4 and CD8 T cells and on B220+IgMintCD21/35int follicular B cells. Notably, B220+GL7hiCD38lo germinal center B cells were IL-27Rlo pretransplant but up-regulated IL-27R expression by d. 7 posttranspant suggesting that IL-27 may directly affect this cell subset in the course of anti-donor humoral immune response
*Conclusions: Our data indicate that IL-27 plays a key role in the generation of donor-specific alloantibodies and may be an attractive therapeutic target to control anti-donor B cell responses and antibody mediated transplant rejection.
To cite this abstract in AMA style:Nicosia M, Miyairi S, Fan R, Beavers A, Gorbacheva V, Valujskikh A. Interleukin-27 is Required for Donor Specific Antibody Production in Response to Heart Allograft Transplantation [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/interleukin-27-is-required-for-donor-specific-antibody-production-in-response-to-heart-allograft-transplantation/. Accessed June 19, 2021.
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