Hansal S A, Morris D I, Sechler J M, Love P E, Rosenberg A S
Laboratory of Immunology, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA.
J Immunol. 1998 Aug 1;161(3):1063-8.
We explored a novel approach to tolerance induction by the transplantation of bone marrow (BM) cells (BMCs) that themselves do not express a foreign histocompatibility Ag, but which give rise to mature lymphocytes that do so. Lines of transgenic (FVB) mice were generated that contained an MHC class I Dd cDNA regulated by a CD2 promoter. Because the CD2 promoter is lymphocyte-specific and activated relatively late in lymphocyte ontogeny, Dd is expressed on most mature lymphocytes in the periphery but only on developing B cells in the BM of transgenic mice. Transgenic BMCs are tolerogenic and reproducibly engraft in nontransgenic mice using a conditioning regimen that is nonpermissive for the engraftment of conventional (MHC promoter) Dd-transgenic BMCs. Engrafted BMCs generate transgene-expressing lymphocytes and confer a state of Ag-specific hyporesponsiveness on the host that is primarily attributable to a peripheral mechanism. The strategies by which tolerance can be optimized in this system are discussed.
我们探索了一种诱导免疫耐受的新方法，即移植骨髓（BM）细胞（BMC），这些细胞本身不表达外来组织相容性抗原，但能产生表达此类抗原的成熟淋巴细胞。构建了转基因（FVB）小鼠品系，其含有受CD2启动子调控的MHC I类Dd cDNA。由于CD2启动子具有淋巴细胞特异性，且在淋巴细胞发育过程中激活相对较晚，因此Dd在外周大多数成熟淋巴细胞上表达，但仅在转基因小鼠骨髓中发育中的B细胞上表达。转基因BMC具有免疫耐受性，使用对传统（MHC启动子）Dd转基因BMC植入不允许的预处理方案，可在非转基因小鼠中反复植入。植入的BMC产生表达转基因的淋巴细胞，并赋予宿主一种抗原特异性低反应状态，这主要归因于外周机制。本文讨论了在该系统中优化免疫耐受的策略。
