Lopez Maria C, Watson Ronald R
Health Promotion Sciences, Enid and Mel Zuckerman College of Public Health, The University of Arizona, Tucson, AZ 85724, USA.
Clin Dev Immunol. 2005 Dec;12(4):249-57. doi: 10.1080/17402520500303339.
In this study, mouse MLN cells and thymocytes from advanced stages of LP-BM5 retrovirus infection were studied. A decrease in the percentage of IL-7(+) cells and an increase in the percentage of IL-16(+) cells in the MLN indicated that secretion of these cytokines was also altered after LP-BM5 infection. The percentage of MLN T cells expressing IL-7 receptors was significantly reduced, while the percentage of MLN T cells expressing TNFR-p75 and of B cells expressing TNFR-p55 increased. Simultaneous analysis of surface markers and cytokine secretion was done in an attempt to understand whether the deregulation of IFN-gamma secretion could be ascribed to a defined cell phenotype, concluding that all T cell subsets studied increased IFN-gamma secretion after retrovirus infection. Finally, thymocyte phenotype was further analyzed trying to correlate changes in thymocyte phenotype with MLN cell phenotype. The results indicated that the increase in single positive either CD4(+)CD8(-) or CD4(-)CD8(+) cells was due to accumulation of both immature (CD3(-)) and mature (CD3(+)) single positive thymocytes. Moreover, single positive mature thymocytes presented a phenotype similar to the phenotype previously seen on MLN T cells. In summary, we can conclude that LP-BM5 uses the immune system to reach the thymus where it interferes with the generation of functionally mature T cells, favoring the development of T cells with an abnormal phenotype. These new T cells are activated to secrete several cytokines that in turn will favor retrovirus replication and inhibit any attempt of the immune system to control infection.
在本研究中,对感染LP - BM5逆转录病毒晚期的小鼠肠系膜淋巴结(MLN)细胞和胸腺细胞进行了研究。MLN中IL - 7(+)细胞百分比下降,IL - 16(+)细胞百分比增加,这表明LP - BM5感染后这些细胞因子的分泌也发生了改变。表达IL - 7受体的MLN T细胞百分比显著降低,而表达TNFR - p75的MLN T细胞百分比以及表达TNFR - p55的B细胞百分比增加。对表面标志物和细胞因子分泌进行同步分析,试图了解IFN - γ分泌失调是否可归因于特定的细胞表型,结果表明,所有研究的T细胞亚群在逆转录病毒感染后IFN - γ分泌均增加。最后,进一步分析胸腺细胞表型,试图将胸腺细胞表型变化与MLN细胞表型相关联。结果表明,CD4(+)CD8(-)或CD4(-)CD8(+)单阳性细胞的增加是由于未成熟(CD3(-))和成熟(CD3(+))单阳性胸腺细胞的积累。此外,单阳性成熟胸腺细胞呈现出与先前在MLN T细胞上所见表型相似的表型。总之,我们可以得出结论,LP - BM5利用免疫系统到达胸腺,在那里干扰功能成熟T细胞的生成,有利于具有异常表型的T细胞的发育。这些新的T细胞被激活以分泌多种细胞因子,进而有利于逆转录病毒复制,并抑制免疫系统控制感染的任何尝试。