NDLI: Regulatory T Cells Are Critical to Tolerance Induction in Presensitized Mouse Transplant Recipients Through Targeting Memory T Cells

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Regulatory T Cells Are Critical to Tolerance Induction in Presensitized Mouse Transplant Recipients Through Targeting Memory T Cells

Content Provider	Scilit
Author	Ge, W. Jiang, J. Liu, W. Lian, D. Saito, A. Garcia, B. Li, X. C. Wang, H.
Copyright Year	2010
Description	Journal: American Journal of Transplantation Memory T cells are a significant barrier to induction of transplant tolerance. However, reliable means to target alloreactive memory T cells have remained elusive. In this study, presensitization of BALB/c mice with C57BL/6 skin grafts generated a large number of $OX40^{+}CD44^{hi}$effector/memory T cells and resulted in rapid rejection of donor heart allografts. Recognizing that anti‐OX40L monoclonal antibody (mAb) (α‐OX40L) monotherapy prolonged graft survival through inhibition and apoptosis of memory T cells in presensitized recipients, α‐OX40L was added to the combined treatment protocol of LF15–0195 (LF) and anti‐CD45RB (α‐CD45RB) mAb—a protocol that induced heart allograft tolerance in non‐presensitized recipients but failed to induce tolerance in presensitized recipients. Interestingly, this triple therapy restored donor‐specific heart allograft tolerance in our presensitized model that was associated with induction of tolerogenic dendritic cells and $CD4^{+}CD25^{+}Foxp3^{+}$ T regulatory cells (Tregs). Of note, $CD25^{+}$ T cell depletion in triple therapy recipients prevented establishment of allograft tolerance. In addition, adoptive transfer of donor‐primed effector/memory T cells into tolerant recipients markedly reduced levels of Tregs and broke tolerance. Our findings indicated that targeting memory T cells, by blocking OX40 costimulation in presensitized recipients was very important to expansion of Tregs, which proved critical to development of tolerance.
Related Links	https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1600-6143.2010.03186.x
Ending Page	1773
Page Count	14
Starting Page	1760
e-ISSN	16006143
DOI	10.1111/j.1600-6143.2010.03186.x
Journal	American Journal of Transplantation
Issue Number	8
Volume Number	10
Language	English
Publisher	Wiley-Blackwell
Publisher Date	2010-07-15
Access Restriction	Open
Subject Keyword	Journal: American Journal of Transplantation Allograft Tolerance Regulatory T Cells Sensitized Recipients
Content Type	Text
Resource Type	Article

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