T Cell And B Cell Tolerance To Galα1,3gal-expressing Heart Xenografts Is Achieved In α1,3-galactosyltransferase-deficient Mice By Nonmyeloablative Induction Of Mixed Chimerism1
T Cell And B Cell Tolerance To Galα1,3gal-expressing Heart Xenografts Is Achieved In α1,3-galactosyltransferase-deficient Mice By Nonmyeloablative Induction Of Mixed Chimerism1
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通过混合嵌合的非清髓性诱导，在 α1,3-半乳糖基转移酶缺陷小鼠中实现了 T 细胞和 B 细胞对表达 Galα1,3gal 的心脏异种移植物的耐受1
DOI：
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发表时间：
2001
期刊：
影响因子：
--
通讯作者：
M. Sykes
中科院分区：
文献类型：
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作者：
H. Ohdan;Yong;K. Swenson;H. Kitamura;M. Sykes
Background, We have previously demonstrated that mixed xenogeneic chimerism and donor-specific T-cell tolerance can be induced in the rat-to-mouse species combination by using a relatively nontoxic, nonmyeloablative conditioning regimen. However, natural antibodies (NAbs) against Galα1,3Gal (Gal) pose an additional major barrier to pig-to-human vascularized xenograft acceptance. Methods. To determine whether the mixed chimerism approach could also overcome this humoral barrier, T cell-depleted rat (GalT +/+ ) bone marrow cells (BMC) were transplanted to α1,3-galactosyltransferase deficient (GalT -/- ) mice conditioned with a nonmyeloablative regimen, consisting of transient T cell and natural killer (NK) cell depletion, 3 Gy whole body irradiation, and 7 Gy thymic irradiation. Results. By giving a high dose (180 × 10 6 ) of rat BMC, persistent mixed chimerism could be induced in GalT -/- mice, although the level of donor-type hematopoietic repopulation declined over time. Induction of mixed chimerism was associated with a rapid disappearance of anti-Gal and anti-rat NAb in the sera. Both anti-Gal Ab-producing cells and B cells with receptors recognizing Gal were undetectable in mixed chimeras, even when the chimerism levels declined, suggesting that a very low level of chimerism could effectively maintain B-cell tolerance to Gal, probably by clonal deletion and/or receptor editing. Mixed chimeras accepted subsequently transplanted donor-type rat hearts (>100 days) without immunosuppressive therapy, whereas delayed vascular and even hyperacute rejection of rat hearts occurred in conditioned control GalT -/- mice. Cellular rejection occurred by 5-6 days in conditioned control wild-type mice. Conclusions. These findings demonstrate that induction of mixed chimerism with a nonmyeloablative regimen can prevent vascularized xenograft rejection by cellular and anti-Gal Ab-dependent pathways in GalT +/+ -to-GalT -/- species combinations.
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体内 T 细胞耗竭可增强 α1,3-半乳糖基转移酶缺陷小鼠体内抗 GALα1,3GAL 天然抗体的产生。
影响因子：
6.2
作者：
Ohdan,H;Yang,YG;Swenson,KG;Thall,AD;Sykes,M
通讯作者：
Sykes,M
影响因子：
6.2
作者：
Chen, AM;Zhou, Y;Yang, YG
通讯作者：
Yang, YG
影响因子：
4.4
作者：
M. Sarmiento;A. Glasebrook;F. Fitch
通讯作者：
M. Sarmiento;A. Glasebrook;F. Fitch
通过单克隆抗体 GK1.5 鉴定的鼠 T 细胞表面分子（称为 L3T4）的特征：L3T4 与人 Leu-3/T4 分子的相似性。
DOI：
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发表时间：
1983
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Dialynas,DP;Quan,ZS;Wall,KA;Pierres,A;Quintans,J;Loken,MR;Pierres,M;Fitch,FW
通讯作者：
Fitch,FW
影响因子：
6.2
作者：
LEVENTHAL, JR;DALMASSO, AP;BAUMGARTNER
通讯作者：
BAUMGARTNER