Neeson Paul, Boyer Jean, Kumar Sanjeev, Lewis Mark G, Mattias Lennox, Veazey Ron, Weiner David, Paterson Yvonne
Microbiology Department, University of Pennsylvania, 323 Johnson Building, 3610 Hamilton Walk, Philadelphia, PA 19104, USA.
Virology. 2006 Oct 25;354(2):299-315. doi: 10.1016/j.virol.2006.06.036. Epub 2006 Aug 9.
In this study in Rhesus macaques, we tested whether IL-12 or IL-15 in a DNA prime-oral Listeria boost amplifies the SIV-Gag-specific CD8 mucosal response. SIV-specific CD8 T cells were demonstrated in the peripheral blood (PB) in all test vaccine groups, but not the control group. SIV-Gag-specific CD8 T cells in the PB expressed alpha4beta7 integrin, the gut-homing receptor; a minor subset co-express alphaEbeta7 integrin. SIV-Gag-specific CD8 T cells were also detected in the gut tissue, intraepithelial (IEL) and lamina propria lymphocytes (LPL) of the duodenum and ileum. These cells were characterized by high levels of beta7 integrin expression and a predominance of the effector memory phenotype. Neither Il-12 nor IL-15 amplified the frequency of SIV-specific CD8 T cells in the gut. Thus, the DNA prime-oral Listeria boost strategy induced a mucosal SIV-Gag-specific CD8 T cell response characterized by expression of the alpha4beta7 integrin gut-homing receptor.
在这项针对恒河猴的研究中,我们测试了DNA初免-口服李斯特菌加强免疫方案中的白细胞介素-12(IL-12)或白细胞介素-15(IL-15)是否会增强针对猿猴免疫缺陷病毒(SIV)-Gag的黏膜CD8细胞反应。在所有测试疫苗组的外周血(PB)中均检测到了SIV特异性CD8 T细胞,但在对照组中未检测到。外周血中针对SIV-Gag的CD8 T细胞表达肠道归巢受体α4β7整合素;一小部分细胞还共表达αEβ7整合素。在十二指肠和回肠的肠道组织、上皮内淋巴细胞(IEL)和固有层淋巴细胞(LPL)中也检测到了针对SIV-Gag的CD8 T细胞。这些细胞的特征是β7整合素表达水平高,且以效应记忆表型为主。IL-12和IL-15均未增加肠道中SIV特异性CD8 T细胞的频率。因此,DNA初免-口服李斯特菌加强免疫策略诱导了一种黏膜SIV-Gag特异性CD8 T细胞反应,其特征是表达α4β7整合素肠道归巢受体。