Pregnancy can induce priming of cytotoxic T lymphocytes specific for paternal HLA antigens that is associated with antibody formation
Pregnancy can induce priming of cytotoxic T lymphocytes specific for paternal HLA antigens that is associated with antibody formation
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DOI：
10.1097/00007890-199609150-00023
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发表时间：
1996-09-15
期刊：
影响因子：
6.2
通讯作者：
Class, FHJ
中科院分区：
文献类型：
--
作者：
Bouma, GJ;vanCaubergh, P;Class, FHJ
一些移植中心认为等待肾移植的母亲不能接受父亲的HLA抗原不匹配。人们担心，怀孕可能会引起母体针对父亲HLA抗原的免疫反应，如果女性接受的器官与父亲的HLA抗原相同，则移植排斥的风险可能会增加。众所周知，一些女性由于怀孕，会产生针对父亲HLA抗原的抗体。本研究的目的是调查怀孕是否也能启动细胞免疫反应，以及这种情况是否在所有情况下都会发生。母体细胞毒性T淋巴细胞定向于父本HLA抗原的频率通过限制性稀释分析试验进行评估，并与针对第三方HLA抗原的频率进行比较，分别在抗cd8缺失和存在的情况下，通过这些试验区分初始和体内启动的细胞毒性T淋巴细胞。与针对第三方HLA抗原的细胞毒性T淋巴细胞相比，针对父本HLA抗原的细胞毒性T淋巴细胞对抗cd8阻断的频率和敏感性没有差异，但针对父本HLA抗原的细胞毒性T淋巴细胞反应更为异质性。因此，将已遗传给儿童的父本抗原与未遗传的父本抗原分开分析。此外，考虑到妊娠诱导的HLA抗体的存在，对从未遗传的父本抗原和那些遗传但未诱导抗体形成的父本抗原检测到初始细胞毒性T淋巴细胞反应。相反，与对第三方抗原的反应相比，在母亲体内诱导HLA特异性抗体的遗传父本抗原会导致细胞毒性T淋巴细胞前体频率升高。发现细胞毒性T淋巴细胞对抗cds的抑制更有抵抗力，这表明这些细胞已经在体内被激活。这些结果表明，并非所有的父本HLA抗原都被认为是不可接受的错配，只有那些与父本HLA抗原相同的个体，其母亲已形成HLA特异性同种抗体，才应被排除在器官捐献之外。
Some transplant centers consider paternal HLA antigens as unacceptable mismatches for mothers awaiting kidney transplantation. It is feared that a pregnancy may cause priming of the maternal immune response directed toward paternal HLA antigens, Should a woman receive an organ from a donor who shares those paternal HLA antigens, the risk of graft rejection might be increased, It is known that some women, as a consequence of pregnancy, develop antibodies specific for paternal HLA antigens, The purpose of the present study was to investigate whether a pregnancy can also prime the cellular immune response and whether this occurs in all cases. Frequencies of maternal cytotoxic T lymphocytes directed to paternal HLA antigens were evaluated in limiting dilution analysis assays and compared with those directed to third-party HLA antigens, Differentiation between naive and in vivo primed cytotoxic T lymphocytes was made by performing these assays in the absence and presence of anti-CD8, respectively. No difference in the frequency nor sensitivity to blocking by anti-CD8 was found when maternal cytotoxic T lymphocytes directed toward paternal HLA antigens were compared with those against third-party HLA antigens, However, more heterogeneous responses were detected against paternal HLA antigens. Therefore, paternal antigens that had been inherited by children were analyzed separately from the paternal antigens that had not been inherited. Furthermore, the presence of pregnancy-induced HLA antibodies was taken into consideration, Naive cytotoxic T lymphocyte responses were detected against paternal antigens that had never been inherited and those that had been inherited but had not induced antibody formation, In contrast, inherited paternal antigens that had induced HLA-specific antibodies in the mother gave rise to elevated cytotoxic T lymphocyte precursor frequencies, as compared with the response to third-party antigens, Also, the cytotoxic T lymphocytes were found to be more resistant to inhibition by anti-CDS, suggesting that these cells had been primed in vivo. These results suggest that not all paternal HLA antigens have to be considered as unacceptable mismatches, Only those individuals who share a paternal HLA antigen against which a mother has formed HLA-specific alloantibodies should be excluded from organ donation.