Babaahmady Kaboutar, Bergmeier Lesley A, Whittall Trevor, Singh Mahavir, Wang Yufei, Lehner Thomas
Peter Gorer Department of Immunobiology, Guy's, King's and St. Thomas' Hospital Medical Schools, London, UK.
J Immunol Methods. 2002 Jun 1;264(1-2):1-10. doi: 10.1016/s0022-1759(02)00002-9.
The capacity of CD8+ and CD4+ T cells and CD14+ monocytes to generate the CC chemokines, RANTES, MIP-1alpha and MIP-1beta, and SIV suppressor factors were studied using cells separated from PBMC of macaques immunized with the 70-kDa heat shock protein (HSP70). Unimmunized macaques showed low levels of the three CC chemokines and SIV-SF, and they showed little variation between PBMC and the two subsets of T cells stimulated with PHA. Immunization with HSP70 elicited an increase in the in vitro concentration of each of the three CC chemokines and SF. This was found with PBMC, CD4+ and CD8+ T cells and to a lesser extent with monocytes, when conventionally separated enriched cell subsets were examined from the same PBMC. However, the concentrations of the three CC chemokines derived from highly purified cell-sorted populations (>95%) were greatly increased, as compared with the enriched cell subsets. The concentration of each of the three chemokines was highest for CD8+ T cells, decreased with CD4+ T cells and was lowest with the CD14+ monocytes, but the latter were not stimulated. Neutralization assays with antibodies to the three CC chemokines showed that the antiviral activity generated by the four populations of cells could be largely accounted for by the three CC chemokines. The results of this comparative study suggests that CD8+ as well as CD4+ T cells and CD14+ monocytes generate the three CC chemokines and SIV-SF when stimulated with a mitogen, and that the baseline innate level can be upregulated by adaptive immune responses to a specific antigen.
利用从用70 kDa热休克蛋白(HSP70)免疫的猕猴外周血单核细胞(PBMC)中分离出的细胞,研究了CD8⁺和CD4⁺ T细胞以及CD14⁺单核细胞产生CC趋化因子、RANTES、MIP-1α和MIP-1β以及猴免疫缺陷病毒(SIV)抑制因子的能力。未免疫的猕猴三种CC趋化因子和SIV抑制因子水平较低,且PBMC与用植物血凝素(PHA)刺激的两个T细胞亚群之间差异不大。用HSP70免疫可使三种CC趋化因子和抑制因子的体外浓度增加。当从同一PBMC中检测常规分离的富集细胞亚群时,PBMC、CD4⁺和CD8⁺ T细胞以及程度较轻的单核细胞均出现这种情况。然而,与富集细胞亚群相比,来自高度纯化的细胞分选群体(>95%)的三种CC趋化因子浓度大幅增加。三种趋化因子中每种趋化因子的浓度在CD8⁺ T细胞中最高,在CD4⁺ T细胞中降低,在CD14⁺单核细胞中最低,但后者未受到刺激。用针对三种CC趋化因子的抗体进行的中和试验表明,这四种细胞群体产生的抗病毒活性在很大程度上可由三种CC趋化因子来解释。这项比较研究的结果表明,CD8⁺以及CD4⁺ T细胞和CD14⁺单核细胞在受到丝裂原刺激时会产生三种CC趋化因子和SIV抑制因子,并且基线固有水平可通过对特定抗原的适应性免疫反应上调。