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Immune Tolerance Monitoring in Renal Allograft Tolerance Induced by Transient Mixed Chimerism in Nonhuman Primates and Humans.

K. Hotta, T. Oura, K. Crisalli, D. Sachs, B. Cosim, T. Kawai.

Center for Transplantation Science, Massachusetts General Hospital, Boston, MA.

Meeting: 2016 American Transplant Congress

Abstract number: D88

Keywords: Kidney transplantation, Mixed chimerism, Monitoring, Tolerance

Session Information

Session Name: Poster Session D: Clinical Science: Tolerance: Clinical Studies

Session Type: Poster Session

Date: Tuesday, June 14, 2016

Session Time: 6:00pm-7:00pm

 Presentation Time: 6:00pm-7:00pm

Location: Halls C&D

Background: Successful induction of allograft tolerance in MHC-mismatched kidney transplantation has been achieved after induction of transient chimerism in both nonhuman primates (NHP) and humans. However, development of a reliable assay to monitor tolerance is critically important to safely taper immunosuppression.

Method: Six NHP and four human recipients of combined kidney and bone marrow transplantation (CKBMT) who achieved long-term renal allograft survival without immunosuppression were studied. Differential T-cell responses were evaluated by CFSE-MLR co-stained for CD4, CD8 and Foxp3.

Results: NHP tolerant recipients evaluated at 2.1±0.9 years after transplantation showed donor-specific CD8+ T cell hyporesponsiveness but displayed vigorous anti-donor CD4+ T cell proliferation. Interestingly, among these proliferated CD4+ cells, significantly higher Foxp3+ cell proliferation was observed against donor, compared with third party stimulators (Fig. A). In contrast, consistently high anti-donor CD8+ and CD4+ T cell responses with limited Treg expansion were observed in rejectors (data not shown). In humans, although assays were performed at markedly later time points (4.7±1.8 years), tolerant patients displayed much greater loss of anti-donor CD8+ and CD4+ T cells responses. However, unlike NHPs, Treg expansion was not significant and CD4+ T cell responses were limited (Fig. B). Finally, we prospectively monitored T cell responses in one recent human CKBMT recipient who achieved renal allograft tolerance. Although anti-donor CD8+ T cell responses gradually disappeared, significant CD4+ responses and Treg expansion were observed at day 325 as observed in most NHP recipients. However, anti-donor Treg responses eventually disappeared by day 727, as observed in other human tolerant recipients (Fig. C).

Conclusion: Regulatory mechanisms were suggested in NHPs at 2 years. More robust loss of anti-donor T cell responses was observed in human tolerant recipients, although these recipients were tested at later time points than the NHP.

CITATION INFORMATION: Hotta K, Oura T, Crisalli K, Sachs D, Cosim B, Kawai T. Immune Tolerance Monitoring in Renal Allograft Tolerance Induced by Transient Mixed Chimerism in Nonhuman Primates and Humans. Am J Transplant. 2016;16 (suppl 3).

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To cite this abstract in AMA style:

Hotta K, Oura T, Crisalli K, Sachs D, Cosim B, Kawai T. Immune Tolerance Monitoring in Renal Allograft Tolerance Induced by Transient Mixed Chimerism in Nonhuman Primates and Humans. [abstract]. Am J Transplant. 2016; 16 (suppl 3). https://atcmeetingabstracts.com/abstract/immune-tolerance-monitoring-in-renal-allograft-tolerance-induced-by-transient-mixed-chimerism-in-nonhuman-primates-and-humans/. Accessed May 9, 2025.

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