Laopajon Witida, Cheyasawan Passaworn, Pata Supansa, Takheaw Nuchjira, Kasinrerk Watchara
Division of Clinical Immunology, Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand.
Biomedical Technology Research Center, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency at the Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand.
Asian Pac J Allergy Immunol. 2023 Jun 11. doi: 10.12932/AP-150123-1532.
CD4, a leukocyte surface glycoprotein, is mainly expressed on CD4+ T cells, but is also expressed on monocytes. The difference in the expression level and structure of CD4 on T cells and monocytes predicts the different functions of this molecule in both cell types. Although the function of CD4 on T cells is well characterized, little is known about that expressed on primary monocytes.
In this study, we investigated the immunoregulation function of CD4 on peripheral blood monocytes.
Methods: CD4 molecule on monocyte was ligated by anti-CD4 monoclonal antibody (mAb), MT4/3. The effect of mAb MT4/3 on T cell proliferation, cytokine production, the expression of monocyte costimulatory molecules, monocyte migration, and macrophage differentiation were investigated. Moreover, the molecular weight of CD4 on peripheral blood monocyte was carried out by Western immunoblotting.
We demonstrated that mAb MT4/3 inhibited anti-CD3 induced T cell proliferation, cytokine production, and the expression of monocyte costimulatory molecules. The ligation of only CD4 on monocytes was sufficient to inhibit T cell activation. Moreover, mAb MT4/3 could inhibit monocyte migration in a transwell migration assay, but not affect the differentiation of monocytes to macrophages. Using purified primary monocytes, the molecular weight of CD4 expressed on monocytes was identified as 55 kDa.
The CD4 molecule expressed on monocytes might play an important role in the regulation of immune responses in both innate and adaptive immunity. Understanding the novel role of CD4 on monocytes in immunoregulation is valuable in the development of new therapeutic approaches.
CD4是一种白细胞表面糖蛋白,主要表达于CD4+T细胞,但也表达于单核细胞。T细胞和单核细胞上CD4表达水平和结构的差异预示着该分子在两种细胞类型中具有不同功能。尽管CD4在T细胞上的功能已得到充分表征,但对于原代单核细胞上表达的CD4却知之甚少。
在本研究中,我们探究了CD4在外周血单核细胞上的免疫调节功能。
用抗CD4单克隆抗体(mAb)MT4/3连接单核细胞上的CD4分子。研究mAb MT4/3对T细胞增殖、细胞因子产生、单核细胞共刺激分子表达、单核细胞迁移和巨噬细胞分化的影响。此外,通过蛋白质免疫印迹法检测外周血单核细胞上CD4的分子量。
我们证明mAb MT4/3可抑制抗CD3诱导的T细胞增殖、细胞因子产生以及单核细胞共刺激分子的表达。仅连接单核细胞上的CD4就足以抑制T细胞活化。此外,在transwell迁移实验中,mAb MT4/3可抑制单核细胞迁移,但不影响单核细胞向巨噬细胞的分化。利用纯化的原代单核细胞,鉴定出单核细胞上表达的CD4分子量为55 kDa。
单核细胞上表达的CD4分子可能在固有免疫和适应性免疫的免疫反应调节中发挥重要作用。了解CD4在单核细胞免疫调节中的新作用对于开发新的治疗方法具有重要价值。