Mee Edward T, Stebbings Richard, Hall Joanna, Giles Elaine, Almond Neil, Rose Nicola J
Division of Virology, National Institute for Biological Standards and Control, Medicines and Healthcare products Regulatory Agency, South Mimms, Hertfordshire, United Kingdom.
Division of Biotherapeutics, National Institute for Biological Standards and Control, Medicines and Healthcare products Regulatory Agency, South Mimms, Hertfordshire, United Kingdom.
PLoS One. 2014 Feb 11;9(2):e88670. doi: 10.1371/journal.pone.0088670. eCollection 2014.
The detailed study of immune effector mechanisms in primate models of infectious disease has been limited by the inability to adoptively transfer lymphocytes from vaccinated animals into naïve immunocompetent recipients. Recent advances in our understanding of the Major Histocompatibility Complex diversity of Mauritian cynomolgus macaques enabled the establishment of a breeding program to generate Major Histocompatibility Complex (MHC)-identical animals. The current study utilised this resource to achieve an improved model of adoptive transfer of lymphocytes in macaques. The effect of route of transfusion on persistence kinetics of adoptively transferred lymphocytes was evaluated in an autologous transfer system. Results indicated that peripheral persistence kinetics were comparable following infusion by different routes, and that cells were detectable at equivalent levels in lymphoid tissues six weeks post-infusion. In a pilot-scale experiment, the persistence of adoptively transferred lymphocytes was compared in MHC-identical siblings and MHC-identical unrelated recipients. Lymphocytes transferred intra-peritoneally were detectable in the periphery within one hour of transfer and circulated at detectable levels in the periphery and lymph nodes for 10 days. Donor lymphocytes were detectable at higher levels in MHC-identical siblings compared with unrelated animals, however the total time of persistence did not differ. These results demonstrate a further refinement of the lymphocyte adoptive transfer system in Mauritian cynomolgus macaques and provide a foundation for hitherto impractical experiments to investigate mechanisms of cellular immunity in primate models of infectious disease.
在传染病灵长类动物模型中，对免疫效应机制的详细研究一直受到限制，因为无法将接种疫苗动物的淋巴细胞过继转移到未接触过抗原的具有免疫能力的受体体内。我们对毛里求斯食蟹猕猴主要组织相容性复合体多样性的最新认识进展，使得建立一个育种计划以培育主要组织相容性复合体（MHC）相同的动物成为可能。当前的研究利用了这一资源，以实现猕猴淋巴细胞过继转移的改进模型。在自体转移系统中评估了输血途径对过继转移淋巴细胞持续动力学的影响。结果表明，不同途径输注后外周血持续动力学相当，并且在输注后六周，在淋巴组织中可检测到细胞处于相当水平。在一个小规模实验中，比较了MHC相同的同胞和MHC相同的非亲属受体中过继转移淋巴细胞的持续情况。腹腔内转移的淋巴细胞在转移后一小时内在外周血中可检测到，并在外周血和淋巴结中以可检测水平循环10天。与非亲属动物相比，在MHC相同的同胞中供体淋巴细胞可检测到的水平更高，然而持续的总时间并无差异。这些结果证明了毛里求斯食蟹猕猴淋巴细胞过继转移系统的进一步完善，并为迄今不切实际的实验提供了基础，以研究传染病灵长类动物模型中的细胞免疫机制。
