Session Time: 3:15pm-4:00pm
Presentation Time: 3:30pm-4:00pm
*Purpose: Preformed donor-specific anti-human leukocyte antigen antibodies (DSAs) have been associated with detrimental effects in transplant recipients. To eliminate preformed DSAs, we desensitized DSA-positive recipients by injecting anti-CD20 monoclonal antibodies (mAbs) and then performed plasmapheresis using a protocol for ABO-incompatible (ABO-I) transplant recipients. However, in contrast to ABO-I transplant recipients who did not affect anti-donor CD4+T-cell responses, hyper responses of anti-donor CD4+T-cell were observed in DSA-positive recipients after desensitization therapy. In this study, we investigated the effect of anti-CD20 mAb-mediated B-cell depletion on anti-donor T-cell responses and the inhibitory role of B-cells in a highly sensitized transplant model.
*Methods: Naïve Balb/c mice were transplanted with C57BL/6 skin grafts (twice; day 0, 14) to prepare a highly sensitized model. On day 42, sensitized Balb/c mice were injected with anti-CD20 mAb to eliminate B-cells (desensitization group). Seven days after the injection (day49), a mixed lymphocyte reaction assay using a carboxyfluorescein succinimidyl ester-labeling technique (CFSE-MLR) were performed to evaluate the effect of B-cell depletion on anti-donor T-cell responses. The control group was administered with isotype-matched control antibodies. Furthemore, to investigate the inhibitory effects of B-cells, CD19+whole B-cells, B1(CD5+CD19+) cells and non B1(CD5–CD19+) cells were co-cultured in CFSE-MLR assay of desensitization group respectively, and the effect of various B-cell subsets on anti-donor T-cell responses were evaluated.
*Results: The average stimulation index (SI) values for the CD4+T-cell responses to donor stimulation were significantly higher in the desensitization group than those in the control group. When co-cultured with various B-cells in CFSE-MLR assay of the desensitization group, the addition of whole CD19+B-cells and B1-cells significantly suppressed the anti-donor CD4+T-cell responses. However, the addition of non B1-cells did not suppress the anti-donor CD4+T-cell responses.
*Conclusions: These findings demonstrate that B-cell depletion with anti-CD20 mAb exacerbates anti-donor CD4+T-cell responses in a highly sensitized transplant model. It might be possible that the sensitized CD5+ CD19+B1-cells have an ability to inhibit anti-donor CD4+T-cell responses.
To cite this abstract in AMA style:Tanaka A, Ide K, Tanaka Y, Ohira M, Tahara H, Morimoto H, Ohdan H. B Cell Depletion with Anti-CD20 mAb Exacerbates Anti-Donor CD4+ T Cell Responses in Highly Sensitized Transplant Model [abstract]. Am J Transplant. 2020; 20 (suppl 3). https://atcmeetingabstracts.com/abstract/b-cell-depletion-with-anti-cd20-mab-exacerbates-anti-donor-cd4-t-cell-responses-in-highly-sensitized-transplant-model/. Accessed September 25, 2021.
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