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普通狒狒和无特定病原体(SPF)橄榄狒狒细胞免疫反应的比较分析()

Comparative Analysis of Cellular Immune Responses in Conventional and SPF Olive Baboons ().

作者信息

Magden Elizabeth R, Nehete Bharti P, Chitta Sriram, Williams Lawrence E, Simmons Joe H, Abee Christian R, Nehete Pramod N

机构信息

The University of Texas MD Anderson Cancer Center Bastrop, Department of Comparative Medicine, Houston, Texas.

The University of Texas MD Anderson Cancer Center Bastrop, Department of Comparative Medicine, Houston, Texas;, Email:

出版信息

Comp Med. 2020 Apr 1;70(2):160-169. doi: 10.30802/AALAS-CM-19-000035. Epub 2020 Feb 3.

Abstract

Olive baboons () have provided a useful model of human diseases and conditions, including cardiac, respiratory, and infectious diseases; diabetes; and involving genetics, immunology, aging, and xenotransplantation. The development of a immunologically defined SPF baboons has advanced research further, especially for studies involving the immune system and immunosuppression. In this study, we compare normal immunologic changes of PBMC subsets, and their function in age-matched conventional and SPF baboons. Our results revealed that both groups have comparable numbers of different lymphocyte subsets, but phenotypic differences in central and effector memory T-cell subsets are more pronounced in CD4+ T cells. Despite equal proportions of CD3+ T cells among the conventional and SPF baboons, PBMC from the conventional group showed greater proliferative responses to phytohemagglutinin and pokeweed mitogen and higher numbers of IFNγ-producing cells after stimulation with concanavalin A or pokeweed mitogen, whereas plasma levels of the inflammatory cytokine TNFα were significantly higher in SPF baboons. Exposure of PBMC from conventional baboons to various Toll-like (TLR) ligands, including TLR3, TLR4, and TLR8, yielded increased numbers of IFNγ producing cells, whereas PBMC from SPF baboons stimulated with TLR5 or TLR6 ligand had more IFNγ-producing cells. These findings suggest that although lymphocyte subsets share many phenotypic and functional similarities in conventional and SPF baboons, specific differences in the immune function of lymphocytes could differentially influence the quality and quantity of their innate and adaptive immune responses. These differences should be considered in interpreting experimental outcomes, specifically in studies measuring immunologic endpoints.

摘要

橄榄狒狒()为人类疾病和病症提供了一个有用的模型,包括心脏、呼吸和传染病;糖尿病;以及涉及遗传学、免疫学、衰老和异种移植等方面。免疫定义的无特定病原体(SPF)狒狒的培育进一步推动了研究,特别是对于涉及免疫系统和免疫抑制的研究。在本研究中,我们比较了年龄匹配的传统狒狒和SPF狒狒外周血单个核细胞(PBMC)亚群的正常免疫变化及其功能。我们的结果显示,两组不同淋巴细胞亚群的数量相当,但中央和效应记忆T细胞亚群的表型差异在CD4 + T细胞中更为明显。尽管传统狒狒和SPF狒狒中CD3 + T细胞的比例相等,但传统组的PBMC对植物血凝素和商陆有丝分裂原表现出更强的增殖反应,在用刀豆蛋白A或商陆有丝分裂原刺激后产生干扰素γ的细胞数量更多,而SPF狒狒中炎症细胞因子肿瘤坏死因子α的血浆水平显著更高。将传统狒狒的PBMC暴露于各种Toll样受体(TLR)配体,包括TLR3、TLR4和TLR8,会使产生干扰素γ的细胞数量增加,而用TLR5或TLR6配体刺激的SPF狒狒的PBMC产生干扰素γ的细胞更多。这些发现表明,尽管传统狒狒和SPF狒狒的淋巴细胞亚群在许多表型和功能上具有相似性,但淋巴细胞免疫功能的特定差异可能会对其固有免疫和适应性免疫反应的质量和数量产生不同影响。在解释实验结果时,尤其是在测量免疫终点的研究中,应考虑这些差异。

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