IN VITRO AND IN VIVO ENHANCEMENT OF MIXED LYMPHOCYTE CULTURE REACTIVITY BY THYMOSIN IN PATIENTS WITH PRIMARY IMMUNODEFICIENCY DISEASE
IN VITRO AND IN VIVO ENHANCEMENT OF MIXED LYMPHOCYTE CULTURE REACTIVITY BY THYMOSIN IN PATIENTS WITH PRIMARY IMMUNODEFICIENCY DISEASE
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胸腺肽对原发性免疫缺陷病患者混合淋巴细胞培养反应性的体外和体内增强
DOI：
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发表时间：
1979
影响因子：
5.2
通讯作者：
M. Cowan
中科院分区：
文献类型：
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作者：
D. Wara;D. Barrett;A. Ammann;M. Cowan
除非进行免疫系统的重建，否则患有原发细胞免疫缺陷疾病的患者通常会在出生后的头几年内死于排卵感染。尽管来自相合的组织相合供者的骨髓移植仍然是首选的治疗方法，但这样的供者很少。胎儿器官移植可能会重建胸腺和/或骨髓来源的淋巴细胞功能，但它会使这些患者面临发生移植物抗宿主反应的风险。2因此，无淋巴细胞胸腺组织提取物和培养的胸腺上皮正在被评估为免疫重建的替代方法。3胸腺蛋白组分5含有至少12个多肽，是几种具有免疫增强能力的胸腺提取物之一。胸腺肽F5能部分恢复新生或成年去胸腺小鼠的细胞免疫。6-8小鼠骨髓或脾细胞与胸腺肽组分5孵育后，胸腺衍生淋巴细胞(T细胞)表面抗原的细胞数增加。从原发或继发性细胞免疫缺陷病患者的外周血或骨髓淋巴细胞与胸腺肽组份5.3~9-11孵育后，从某些细胞免疫缺陷患者获得的淋巴细胞在混合淋巴细胞培养(MLC)中对同种异体细胞的反应增强。在过去的4.5年中，我们用胸腺肽组分5治疗了18例各种细胞免疫缺陷疾病。这些患者在开始治疗前有反复感染和对传统治疗无效或T细胞花环形成和/或与胸腺素组分5孵育的MLC反应增强。我们发现，在治疗开始前，淋巴细胞与胸腺肽体外孵育后T细胞花环的形成增加通常预示着治疗后体内T细胞数量的增加。我们观察到，在胸腺肽5组分治疗后，T细胞数量的正常化和T细胞功能的改善之间经常存在不一致。18名接受体内胸腺素治疗的患有各种细胞免疫缺陷的患者的MLC反应是本报告的基础。我们试图回顾MLC反应性的变化
Patients with primary cellular immunodeficiency disease usually die within the first years of life from ovetwhelming infection unless reconstitution of their immune system is carried out. Although bone marrow transplantation from an HLA-identical histocompatible donor remains the preferred therapy, such donors are rarely available. Fetal organ transplantation may reconstitute thymic-derived and/ or bone marrow-derived lymphocyte function,' but it places these patients at risk for developing graft-versus-host reactions.2 Therefore, lymphocyte-free thymic tissue extracts and cultured thymic epithelium are being evaluated as alternative methods of immunoreconstitution.3~ Thymosin fraction 5 , which contains at least 12 polypeptides, is one of several thymic extracts which have immune enhancing capabilities. Thymosin F5 partially restores cellular immunity in neonatal or adult thymectomized mice.6-8 Mouse bone marrow or spleen cell preparations incubated with thymosin fraction 5, have increased numbers of cells bearing thymic-derived lymphocyte (T-cell) surface antigens.', Peripheral blood or bone marrow lymphocytes isolated from patients with primary or secondary cellular immunodeficiency disease form increased numbers of T-cell rosettes after incubation with thymosin fraction 5.3~9-11 Lymphocytes obtained from some patients with cellular immunodeficiency have an enhanced response to allogeneic cells in mixed lymphocyte culture (MLC:) following incubation with thymosin fraction 5. During the past 4.5 years, we have treated 18 patients with various cellular immunodeficiency diseases with thymosin fraction 5. The patients had recurrent infection and no response to traditional therapy or enhanced T-cell rosette formation and/or MLC reactivity with thymosin fraction 5 incubation prior to initiation of therapy. We documented that increased T-cell rosette formation following lymphocyte incubation with thymosin in vitro before the initiation of therapy usually predicted increased T-cell numbers in vivo following therapy. We observed that, following therapy with thymosin fraction 5 , there is often discordance between normalization of T-cell numbers and improvement of T-cell function.*' The MLC reactivity of 18 patients with a variety of cellular immunodeficiencies who have received in vivo thymosin therapy form the basis of this report. We have attempted to retrospectively correlate changes in MLC reactivity