Chen X, Shelton J, McCullagh P
Developmental Physiology Group, John Curtin School of Medical Research, Australian National University, Canberra, Australia.
J Autoimmun. 1995 Aug;8(4):539-59. doi: 10.1016/0896-8411(95)90007-1.
We have devised an experimental strategy to determine whether the developing immune system of normal fetal animals can spontaneously acquire the capacity to inhibit autoimmune responses by its cells as it matures. Whilst the existence of cells with the capacity to exert negative regulation and to curtail autoimmune responses has been demonstrated previously in response to the experimental induction of these responses, the relevance of such regulatory processes to the prevention of overt autoimmunity in normal animals has not been established. We have produced pairs of identical twin fetal lambs by splitting blastocysts and have subsequently deprived one of each pair of exposure to thyroid-specific antigens by surgical thyroidectomy before development of immunological self recognition. Thyroidectomized fetuses developed T lymphocytes autoreactive against self thyrocytes. However, their normal, identical co-twins were found to acquire a class of T lymphocytes with the capacity to block anti-thyrocyte autoreactive cells from the thyroidectomized fetal co-twin. Blocking of anti-thyroid autoreactivity required preliminary contact between these normal T lymphocytes and the target thyrocytes. Substitution of an allograft of fetal thyroid tissue for a fetal lamb's own thyroid gland failed to prevent the development of autoreactivity against autologous thyrocytes by the recipient's lymphocytes. However, the reactivity of those lymphocytes against thyrocytes from the specific allogeneic thyroid donor was markedly curtailed.
我们设计了一种实验策略，以确定正常胎儿动物发育中的免疫系统在成熟过程中是否能够自发地获得其细胞抑制自身免疫反应的能力。虽然先前已证明存在具有负调控能力并能减少自身免疫反应的细胞，这是对这些反应进行实验诱导的结果，但此类调节过程与正常动物预防明显自身免疫的相关性尚未确立。我们通过分割囊胚产生了一对对同卵双生胎儿羔羊，随后在免疫自我识别发育之前，通过手术切除甲状腺，使每对中的一只胎儿不接触甲状腺特异性抗原。甲状腺切除的胎儿发育出针对自身甲状腺细胞的自身反应性T淋巴细胞。然而，发现它们正常的同卵双胞胎获得了一类T淋巴细胞，这类T淋巴细胞能够阻止来自甲状腺切除的胎儿同卵双胞胎的抗甲状腺细胞自身反应性细胞。阻断抗甲状腺自身反应性需要这些正常T淋巴细胞与靶甲状腺细胞进行初步接触。用胎儿甲状腺组织同种异体移植替代胎儿羔羊自身的甲状腺未能阻止受体淋巴细胞针对自身甲状腺细胞产生自身反应性。然而，这些淋巴细胞对来自特定同种异体甲状腺供体的甲状腺细胞的反应性明显降低。
