Tolerance to noninherited maternal MHC antigens in mice
Tolerance to noninherited maternal MHC antigens in mice
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DOI：
10.4049/jimmunol.171.10.5554
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发表时间：
2003-11-15
影响因子：
4.4
通讯作者：
Burlingham, WJ
中科院分区：
文献类型：
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作者：
Andrassy, J;Kusaka, S;Burlingham, WJ
对非遗传性母体抗原（NIMA）的耐受现象知之甚少。为了分析NIMA效应，将C57 BL/6（H-2（B/B））雄性小鼠与B6 D2 F（1）（H-2（B/d））雌性小鼠交配，其中50%的后代是已暴露于母体H-2（d）同种抗原的H-2（B/B）小鼠。对照是C57 BL/6母体的H-2（B/B）后代，近交系C57 BL/6小鼠或来自具有H-2（B/d）父亲的breeding的F1回交小鼠。我们发现，57%的半同种异体（H-2 B/d）母亲的H-2（B/B）后代接受完全同种异体DBA/2（H-2（d/d））心脏移植超过180天，而对照组中相似的移植物在第11天全部被排斥（p < 0.0004）。Foster护理研究表明，这种致耐受性作用需要口服和子宫内暴露于NIMA。还发现NIMA的作用是延长来自半同种异体供体的皮肤移植物的存活（p < 0.02）。脾细胞移植前分析显示，与对照小鼠相比，NIMA（d）暴露小鼠中产生IL-2、IL-5和IFN-γ的T细胞对表达H-2（d）的APC的应答减少了40-90%。静脉注射H-2L（61-80）（d）肽的妊娠BALB/c-dm 2（H-2L（d）阴性）雌性小鼠显著抑制了后代对H-2L（d）的间接途径同种异体反应性CD 4（+）T细胞应答。这些结果表明，胎儿和新生儿自然暴露于母体细胞和/或可溶性MHC抗原抑制了后代的NIMA-同种异体特异性T细胞，从而诱发成年小鼠的器官移植耐受。
The phenomenon of tolerance to noninherited maternal Ags (NIMA) is poorly understood. To analyze the NIMA effect C57BL/6 (H-2(b/b)) males were mated with B6D2F(1) (H-2(b/d)) females, whereby 50% of the offspring are H-2(b/b) mice that have been exposed to maternal H-2(d) alloantigens. Controls were H-2(b/b) offspring of C57BL/6 mothers, either inbred C57BL/6 mice or F, backcross mice from breedings with H-2(b/d) fathers. We found that 57% of the H-2(b/b) offspring of semiallogeneic (H-2b/d) mothers accepted fully allogeneic DBA/2 (H-2(d/d)) heart grafts for >180 days, while similar transplants were all rejected by day 11 in controls (p < 0.0004). Foster nursing studies showed that both oral and in utero exposure to NIMA are required for this tolerogenic effect. An effect of NIMA was also found to extend the survival of skin grafts from a semiallogeneic donor (p < 0.02). Pretransplant analysis of splenocytes showed a 40-90% reduction of IL-2-, IL-5-, and IFN-gamma-producing T cells responding to H-2(d)-expressing APC in NIMA(d)-exposed vs control mice. Injection of pregnant BALB/c-dm2 (H-2L(d)-negative) female mice i.v. with H-2L(61-80)(d) peptide profoundly suppressed the offspring's indirect pathway alloreactive CD4(+) T cell response to H-2L(d). These results suggest that the natural exposure of the fetus and newborn to maternal cells and/or soluble MHC Ags suppresses NIMA-allospecific T cells of the offspring, predisposing to organ transplant tolerance in adult mice.