Session Name: Acute Rejection
Session Date & Time: None. Available on demand.
*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 June 13, 2021.
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