Brosnahan Margaret M, Silvela Emily J, Crumb Jessica, Miller Donald C, Erb Hollis N, Antczak Douglas F
Baker Institute for Animal Health, Cornell University College of Veterinary Medicine, Ithaca, New York.
Department of Population Medicine and Diagnostic Sciences, Cornell University College of Veterinary Medicine, Ithaca, New York.
Biol Reprod. 2016 Dec;95(6):135. doi: 10.1095/biolreprod.115.137851. Epub 2016 Oct 19.
Invasive trophoblast from Day 34 horse conceptuses survives in extrauterine sites in allogeneic recipients that are immunologically naive to donor major histocompatibility complex class I antigens. The ectopic trophoblast retains its in utero characteristics, including similar lifespan, physiologic effect of its secreted product (equine chorionic gonadotropin) upon the recipient's ovaries, and induction of host immune responses. Immunologic memory has not been considered previously in this experimental system. We hypothesized that primary exposure to ectopic trophoblast would affect the recipient's immune status such that the survival time of subsequent transplants would be altered. Secondary transplant lifespans could be shortened by destructive memory responses, as has been observed in ectopic trophoblast studies in rodents, or lengthened, as occurs when male skin grafts follow multiple syngeneic pregnancies in mice. Eight mares received two closely spaced trophoblast transplants. Both grafts for each recipient were obtained from conceptuses sired by the same stallion to provide consistency in histocompatibility antigen exposure. Donor stallions were major histocompatibility complex class I homozygotes. Cytotoxic antibody production was tracked to monitor recipients' immune responses to the transplants. Detection of serum equine chorionic gonadotropin was used as a proxy for transplant lifespan. There was no significant difference between the distributions of primary and secondary transplant lifespans, despite evidence of immunologic memory. These data demonstrate that secondary ectopic trophoblast transplants in horses do not experience earlier destruction or prolonged survival following immune priming of recipients. Mechanisms responsible for the eventual demise of the transplants remain unperturbed by secondary immune responses or chronic antigenic exposure.
来自妊娠34天马胚胎的侵袭性滋养层细胞在对供体主要组织相容性复合体I类抗原免疫幼稚的同种异体受体的子宫外部位存活。异位滋养层细胞保留其在子宫内的特征，包括相似的寿命、其分泌产物（马绒毛膜促性腺激素）对受体卵巢的生理作用以及诱导宿主免疫反应。在此实验系统中，以前未考虑免疫记忆。我们假设初次接触异位滋养层细胞会影响受体的免疫状态，从而改变后续移植的存活时间。继发性移植的寿命可能会因破坏性记忆反应而缩短，如在啮齿动物的异位滋养层细胞研究中所观察到的，或者延长，如在小鼠多次同基因妊娠后进行雄性皮肤移植时所发生的情况。八匹母马接受了两次间隔紧密的滋养层细胞移植。每个受体的两个移植物均取自同一匹种马所生的胚胎，以确保组织相容性抗原暴露的一致性。供体种马是主要组织相容性复合体I类纯合子。追踪细胞毒性抗体的产生以监测受体对移植的免疫反应。检测血清马绒毛膜促性腺激素用作移植寿命的替代指标。尽管有免疫记忆的证据，但原发性和继发性移植寿命的分布之间没有显著差异。这些数据表明，在马中进行继发性异位滋养层细胞移植时，受体免疫致敏后移植不会更早被破坏或延长存活时间。导致移植最终死亡的机制不受继发性免疫反应或慢性抗原暴露的影响。
