B-cell-dependent memory T cells impede nonmyeloablative mixed chimerism induction in presensitized mice.
B-cell-dependent memory T cells impede nonmyeloablative mixed chimerism induction in presensitized mice.
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DOI：
10.1111/j.1600-6143.2011.03683.x
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发表时间：
2011-11
期刊：
影响因子：
--
通讯作者：
Sykes M
中科院分区：
文献类型：
--
作者：
Levesque V;Bardwell PD;Shimizu I;Haspot F;Benichou G;Yeap BY;Sykes M
对HLA抗原的预致敏限制了器官移植的成功。通过混合嵌合体实现供者特异性耐受可改善移植预致敏患者的预后。在预致敏的B细胞缺陷型μMT B6小鼠中，我们开发了非清髓性骨髓移植（BMT）方案，成功耐受了预致敏的T细胞，实现了长期（LT）多谱系嵌合体和对供体型皮肤的耐受。为了在野生型（WT）动物中应用这些方案，同时避免抗体介导的供体骨髓细胞的破坏，使预致敏的WT B6小鼠休息>2年以允许同种抗体清除。然而，嵌合体和耐受性不能可靠地实现LT预致敏WT B6小鼠，其中同种抗体已下降到最低或检测不到的水平之前BMT。强抗供体记忆T细胞反应检测LT预致敏WT B6小鼠发生排斥反应后，供体骨髓（BM），而同种抗体水平始终保持较低。相比之下，与WT B6小鼠相比，预致敏的μMT B6小鼠的记忆T细胞应答减少。这些数据暗示T细胞记忆，而不是同种抗体，在排斥供体BM在LT致敏WT小鼠。
Presensitization to HLA antigens limits the success of organ transplantation. The achievement of donor-specific tolerance via mixed chimerism could improve outcomes of transplantation in presensitized patients. In presensitized B-cell-deficient μMT B6 mice, we developed nonmyeloablative bone marrow transplantation (BMT) regimens that successfully tolerized presensitized T cells, achieving long-term (LT) multilineage chimerism and tolerance to donor-type skin. To apply these regimens in wild-type (WT) animals while avoiding antibody-mediated destruction of donor bone marrow cells, presensitized WT B6 mice were rested >2 years to allow alloantibody clearance. However, chimerism and tolerance were not reliably achieved in LT presensitized WT B6 mice in which alloantibody had declined to minimal or undetectable levels before BMT. Strong antidonor memory T-cell responses were detected in LT presensitized WT B6 mice after rejection of donor bone marrow (BM) occurred, whereas levels of alloantibody remained consistently low. In contrast, presensitized μMT B6 mice had diminished memory T-cell responses compared to WT B6 mice. These data implicate T-cell memory, but not alloantibody, in rejection of donor BM in LT presensitized WT mice.
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影响因子：
20.3
作者：
Taylor, Patricia A.;Ehrhardt, Michael J.;Blazarl, Bruce R.
通讯作者：
Blazarl, Bruce R.
影响因子：
4.4
作者：
Umemura, A;Morita, H;Maki, T
通讯作者：
Maki, T
由非致死性准备方案诱导的混合嵌合和永久特异性移植耐受。
影响因子：
15.3
作者：
Sharabi, Y;Sachs, D H
通讯作者：
Sachs, D H
影响因子：
20.3
作者：
Haspot, Fabienne;Fehr, Thomas;Sykes, Megan
通讯作者：
Sykes, Megan
影响因子：
4.4
作者：
Yuan, XL;Salama, AD;Sayegh, MH
通讯作者：
Sayegh, MH