Makino Yasuhiko, Cook Donald N, Smithies Oliver, Hwang Olivia Y, Neilson Eric G, Turka Laurence A, Sato Hiroshi, Wells Andrew D, Danoff Theodore M
Penn Center for Molecular Studies of Kidney Disease, Renal-Electrolyte and Hypertension Division, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Clin Immunol. 2002 Mar;102(3):302-9. doi: 10.1006/clim.2001.5178.
The chemokine RANTES is a chemoattractant for monocytes and T cells and is postulated to participate in many aspects of the immune response. To evaluate the biological roles of RANTES in vivo, we generated RANTES-deficient (-/-) mice and characterized their T cell function. In cutaneous delayed-type hypersensitivity assays, a 50% reduction in ear and footpad swelling was seen in -/- mice compared to +/+ mice. In vitro, polyclonal and antigen-specific T cell proliferation was decreased. Quantitative analysis using the fluorescent dye carboxy-fluorescein succinimidyl ester revealed that this proliferative defect was due both to fewer antigen-reactive T cells and to a reduction in the capacity of these cells to proliferate. In addition, IFN-gamma and IL-2 production by the -/- T cells was dramatically decreased. Together, these data suggest that RANTES is required for normal T cell functions as well as for recruiting monocytes and T cells to sites of inflammation.
趋化因子RANTES是一种单核细胞和T细胞的化学引诱剂,据推测它参与免疫反应的多个方面。为了评估RANTES在体内的生物学作用,我们培育出了RANTES基因缺陷(-/-)小鼠,并对其T细胞功能进行了表征。在皮肤迟发型超敏反应试验中,与+/+小鼠相比,-/-小鼠的耳部和足垫肿胀减少了50%。在体外,多克隆和抗原特异性T细胞增殖减少。使用荧光染料羧基荧光素琥珀酰亚胺酯进行的定量分析表明,这种增殖缺陷既是由于抗原反应性T细胞数量减少,也是由于这些细胞增殖能力降低所致。此外,-/- T细胞产生的IFN-γ和IL-2显著减少。这些数据共同表明,RANTES对于正常T细胞功能以及将单核细胞和T细胞募集到炎症部位是必需的。