Phenotypic and Functional Characterization of Monoclonal Antibodies with Specificity for Rhesus Macaque CD200, CD200R and Mincle.
Phenotypic and Functional Characterization of Monoclonal Antibodies with Specificity for Rhesus Macaque CD200, CD200R and Mincle.
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DOI：
10.1371/journal.pone.0140689
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Ansari AA
中科院分区：
文献类型：
--
作者：
Byrareddy SN;Little D;Mayne AE;Villinger F;Ansari AA
凝集素样分子及其受体是细胞表面分子，已被证明在促进感染或充当HIV/SIV体内转运蛋白中发挥作用。这些凝集素样分子在HIV/SIV感染发病机制中的作用仍有待进一步研究。为了进一步了解这些凝集素样分子的潜在作用，我们的实验室产生了针对恒河猴CD 200，CD 200 R和Mincle的人类类似物的单克隆抗体（mAb），因为恒河猴被认为是研究人类HIV感染的最可靠的动物模型。本文描述了表达这些凝集素样分子的来自恒河猴的血液和各种组织的细胞谱系的表征。在单核细胞中，恒河猴的髓系细胞是表达容易检测水平的CD 200、CD 200 R和Mincle的主要细胞系，这与我们实验室先前报道的Siglec-1和Siglec-3的表达相似。亚群分析显示，正常恒河猴的CD 14 +/CD 16-亚群表达CD 200、CD 200 R和Mincle的频率较高。注意到来自各种组织的CD 14+细胞的门控群体表达这些分子的频率和密度的差异，其中PBMC和骨髓表达最高，而从结肠和回肠分离的单核细胞表达最低水平。虽然显著频率的pDC和mDC表达Siglec-1/Siglec-3，但在来自恒河猴的PBMC中表达CD 200、CD 200 R和Mincle的频率低得多。抗CD 200和CD 200 R的mAb在体外对嗜巨噬细胞的SIV/SHIV感染有抑制作用，但对Mincle无抑制作用。我们的结论是，这些单克隆抗体可能有潜力被用作连续治疗剂，以控制/抑制SIV/HIV感染。
Lectin-like molecules and their receptors are cell surface molecules that have been shown to play a role in either facilitating infection or serving as transporters of HIV/SIV in vivo. The role of these lectin-like molecules in the pathogenesis of HIV/SIV infection continues to be defined. In efforts to gain further insight on the potential role of these lectin-like molecules, our laboratory generated monoclonal antibodies (mAb) against the human analogs of rhesus macaque CD200, CD200R and Mincle, since the rhesus macaques are accepted as the most reliable animal model to study human HIV infection. The characterization of the cell lineages from the blood and various tissues of rhesus macaques that express these lectin-like molecules are described herein. Among the mononuclear cells, the cells of the myeloid lineage of rhesus macaques are the predominant cell lineages that express readily detectable levels of CD200, CD200R and Mincle that is similar to the expression of Siglec-1 and Siglec-3 reported by our laboratory earlier. Subset analysis revealed that a higher frequency of the CD14+/CD16- subset from normal rhesus macaques express CD200, CD200R and Mincle. Differences in the frequencies and density of expression of these molecules by the gated population of CD14+ cells from various tissues are noted with PBMC and bone marrow expressing the highest and the mononuclear cells isolated from the colon and ileum expressing the lowest levels. While a significant frequency of pDCs and mDCs express Siglec-1/Siglec-3, a much lower frequency expresses CD200, CD200R and Mincle in PBMCs from rhesus macaques. The mAb against CD200 and CD200R but not Mincle appear to inhibit the infection of macrophage tropic SIV/SHIV in vitro. We conclude that these mAbs may have potential to be used as adjunctive therapeutic agents to control/inhibit SIV/HIV infection.