The Efficacy of Delayed Fc-nonbinding Anti-CD3 Antibody Treatment in Sensitized Allogeneic Mouse Heart Transplantation
1Dept. of Gastroenterological Surgery I, Hokkaido University, Sapporo, Japan, 2Dept. of Transplant Surgery, Hokkaido University, Sapporo, Japan, 3Division of Organ Transplantation, Hokkaido University Hospital, Sapporo, Japan
Meeting: 2021 American Transplant Congress
Abstract number: 505
Keywords: CD3, Graft survival, Graft-infiltrating lymphocytes
Topic: Basic Science » Acute Rejection
Session Information
Session Name: Acute Rejection
Session Type: Poster Abstract
Session Date & Time: None. Available on demand.
Location: Virtual
*Purpose: Delayed treatment with Fc-nonbinding anti-CD3 antibody (ab) permits early graft infiltrating cells to promotes a transplant tolerance. However, graft infiltrating cells immediate after transplantation includes alloreactive memory T cells in sensitized situation, which may abrogate a tolerogeneic effect in delayed treatment protocol.
*Methods: Sensitized splenocytes were obtained from recipient C57BL/6 (B6, H2b) mice grafting cardiac allograft from BALB/c (H2d) in 7 to 11 weeks post-transplantation. Naïve B6 mice were adoptively transferred with 15×106 sensitized splenocytes at 2 or 3 days before grafting H2d heart and then treated with delayed anti-CD3F(ab’)2 treatment (anti-CD3F(ab’)2 for 5 days starting from 3 days post-transplantation).
*Results: Early anti-CD3F(ab’)2 treatments for 5 days (day -1 to 3) significantly prolonged graft survival in BALC/c-to-B6 heart transplant model (n=5, median survival time [MST] 38 days , p=0.001 , vs. untreated control). Further, delayed anti-CD3F(ab’)2 treatments for 5 days (day 3 to 7) promoted indefinite graft survival (MST >100 days) which data is consistent with previous reports (Goto R et al., AJT 2012). Then we applied this delayed anti-CD3F(ab’)2 treatment to sensitized mice. Sensitized B6 mice promptly rejected H2d cardiac allografts within 7 days as shown in Figure 1A (n=5, black circles, p=0.003 , vs. B6 mice transferred naïve splenocytes, n=5, MST 8 days, dotted line). We also observed significant increased numbers of sensitized splenocytes were infiltrated within an allograft by CTV staining technique (n=5, p<0.05 vs. naïve cells transferred model). Interestingly, delayed anti-CD3F(ab’)2 treatments efficiently reduced the number of sensitized graft infiltrating cells (Fig.1B) and promoted long-term graft acceptance (n=5, MST>80 days, empty circles in Fig.1A).
*Conclusions: Delayed anti-CD3F(ab’)2 treatment strategy allows long-term graft acceptance despite sensitized situation. In the development of Fc-nonbinding humanized anti-CD3 antibody, our findings would be useful in clinical organ transplantation.
To cite this abstract in AMA style:
Ota T, Goto R, Kanazawa R, Shibuya K, Ganchiku Y, Kawamura N, Watanabe M, Fukai M, Shimamura T, Taketomi A. The Efficacy of Delayed Fc-nonbinding Anti-CD3 Antibody Treatment in Sensitized Allogeneic Mouse Heart Transplantation [abstract]. Am J Transplant. 2021; 21 (suppl 3). https://atcmeetingabstracts.com/abstract/the-efficacy-of-delayed-fc-nonbinding-anti-cd3-antibody-treatment-in-sensitized-allogeneic-mouse-heart-transplantation/. Accessed November 24, 2024.« Back to 2021 American Transplant Congress