Selective Depletion of Alloreactive T Cells Leads to Long-Term Islet Allograft Survival across a Major Histocompatibility Complex Mismatch in Diabetic Mice
| Autor: | M. Hu, J. Wu, G. Y. Zhang, Y. M. Wang, D. Watson, S. Yi, W. J. Hawthorne, P. J. O'connell, S. I. Alexander |
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| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: | |
| Zdroj: | Cell Transplantation, Vol 22 (2013) |
| Druh dokumentu: | article |
| ISSN: | 0963-6897 1555-3892 |
| DOI: | 10.3727/096368912X658025 |
| Popis: | Islet cell transplantation as a therapy for type 1 diabetes has been limited by progressive graft loss. Significant immunosuppression including T-cell ablation has been used in an attempt to limit islet rejection. Here, we show that CD3 + lymphocytes depleted of alloreactive T cells selected from a mixed lymphocyte reaction (MLR), where responder BALB/c splenocytes stained with carboxyfluorescein succinimidyl ester (CFSE) were stimulated with irradiated C57BL/6 splenocytes for 5 days, infused into diabetic immunodeficient mice are capable of restoring a broad T-cell repertoire and specifically do not reject islet transplants from the strain (C57BL/6) used in the original depletion. These mice demonstrate reconstitution with CD4 + and CD8 + T cells, the capacity to reject third-party grafts (CBA), and restoration of interferon-γ (IFN-γ) responses to third-party alloantigens. Over time, both forkhead box P3-positive (Foxp3 + ) T regulatory cells (Tregs) and γδ T cells expand, suggesting a role for peripheral tolerance, in addition to the initial depletion of alloreactive T cells, in long-term islet graft survival. Our results suggest that immune restoration with CD3 + lymphocytes where alloreactive T cells are removed can restore cognate immunity without islet allograft loss and recurrence of diabetes. |
| Databáze: | Directory of Open Access Journals |
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