Development of an animal model for autotransfusion therapy: In vitro characterization and analysis of anti-CD3/CD28 expanded cells
Development of an animal model for autotransfusion therapy: In vitro characterization and analysis of anti-CD3/CD28 expanded cells
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DOI：
10.1097/00042560-199811010-00002
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发表时间：
1998-11-01
期刊：
影响因子：
--
通讯作者：
Ansari, AA
中科院分区：
文献类型：
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作者：
Brice, GT;Riley, JL;Ansari, AA
以前的研究表明，在体外培养的人CD 4（+）T细胞与抗体的CD 3和CD 28固定在珠诱导抗HIV-1感染的作用。在此，我们使用了来自非人灵长类动物的CD 4（+）T细胞来解决使用此类细胞治疗和免疫重建感染HIV和猴免疫病毒（SIV）的人类和非人灵长类动物的关键问题。这些研究包括定义抗病毒作用的动力学，获得性表型的相对稳定性，以及这些活化和扩增的CD 4 + T细胞是否保留其免疫功能。我们的研究结果表明，抗病毒作用是诱导后迅速激活抗CD 3/CD 28包被的弯曲。此外，这些细胞的抗病毒作用并不稳定，需要用抗CD 3/CD 28珠连续培养。从抗-CD 3/CD 28刺激中去除CD 4（+）T细胞使这些细胞对感染易感，表明耐药表型在这些培养物中不稳定。然而，抗CD 3/CD 28扩增的CD 4（+）T细胞确实保留了免疫功能。因此，尽管这些发现意味着为患者提供抗病毒CD 4（+）T细胞的治疗策略需要谨慎，但本研究表明，输注保留免疫功能的此类细胞可能具有免疫恢复能力。
Previous studies have shown that in vitro culture of human CD4(+) T cells with antibodies to CD3 and CD28 immobilized on beads induced an antiviral effect to HIV-1 infection. Herein, we have used CD4(+) T cells from nonhuman primates to address issues critical for use of such cells for therapy and immune reconstitution of humans and nonhuman primates infected with HIV and simian immunovirus (SIV). These studies include definition of the kinetics of the antiviral effect, the relative stability of the acquired phenotype, and whether such activated and expanded CD4+ T cells retain their immune function. Results of our studies show that antiviral effect is induced rapidly following activation with anti-CD3/CD28-coated bends. Additionally, the antiviral effect is not stable in these cells and requires continuous culture with anti-CD3/CD28 beads. Removal of CD4(+) T cells from anti-CD3/CD28 stimulation renders these cells susceptible to infection, demonstrating that the resistant phenotype is not stable in these cultures. However, anti-CD3/CD28 expanded CD4(+) T cells do retain immune function. Thus, although these findings imply a note of caution for therapeutic strategies aimed at providing patients with virus-resistant CD4(+) T cells, the present study suggests that transfusion of such cells with retained immune function may have immune restoration capability.