Lehner T, Panagiotidi C, Bergmeier L A, Tao L, Brookes R, Gearing A, Adams S
Department of Immunology, UMDS of Guy's Hospital, London, United Kingdom.
Adv Exp Med Biol. 1995;371A:357-65. doi: 10.1007/978-1-4615-1941-6_75.
We investigated genital-associated lymphoid tissue (GENALT) in non-human primates (macaques), by augmenting vaginal with oral immunization. The vaccine was a recombinant particulate SIV antigen (p27:Ty-VLP), linked to CT-B, and administered into the vagina by a paediatric naso-gastric tube and into the stomach by a gastric tube. Oro-vaginal or vagino-oral sequence of immunization elicited specific CD4+ T cell proliferative responses to p27 antigen in the genital lymph nodes and the spleen but not in unrelated lymph nodes. CD4+ T cells reconstituted with B cells and macrophages from the genital lymph nodes induced specific IgA and to a lesser extent IgG anti-p27 antibodies. However, the corresponding splenic cells induced greater IgG than IgA antibody synthesis. Intramuscular immunization primed splenic but not genital lymph node cells, and induced CD4+ T cell proliferative responses and predominantly B cell IgG antibody synthesis. Finding primed B and T cells in the genital lymph nodes after augmenting vaginal by oral immunization provides experimental evidence for GENALT in non-human primates. This primate model of vaginal immunization suggests 3 levels of specific immunity: (1) secretory IgA (and IgG) in the cervico-vaginal mucosal epithelium; (2) primed CD4+ T cells and B cells in the genital lymph nodes and the spleen; and (3) circulating CD4+ T cells, B cells and IgG and IgA antibodies specific to the immunizing antigen.
我们通过口服免疫增强阴道免疫,对非人类灵长类动物(猕猴)的生殖道相关淋巴组织(GENALT)进行了研究。疫苗是一种与霍乱毒素B亚单位(CT-B)相连的重组颗粒型猴免疫缺陷病毒(SIV)抗原(p27:Ty-VLP),通过小儿鼻胃管注入阴道,通过胃管注入胃内。经口-阴道或阴道-口免疫顺序在生殖器淋巴结和脾脏中引发了针对p27抗原的特异性CD4⁺T细胞增殖反应,但在无关淋巴结中未引发。用来自生殖器淋巴结的B细胞和巨噬细胞重建的CD4⁺T细胞诱导了特异性IgA,并在较小程度上诱导了IgG抗p27抗体。然而,相应的脾细胞诱导的IgG比IgA抗体合成更多。肌肉注射免疫使脾细胞而非生殖器淋巴结细胞致敏,并诱导了CD4⁺T细胞增殖反应和主要是B细胞IgG抗体合成。经口免疫增强阴道免疫后在生殖器淋巴结中发现致敏的B细胞和T细胞,为非人类灵长类动物的GENALT提供了实验证据。这种阴道免疫的灵长类动物模型提示了三级特异性免疫:(1)宫颈-阴道黏膜上皮中的分泌型IgA(和IgG);(2)生殖器淋巴结和脾脏中的致敏CD4⁺T细胞和B细胞;(3)针对免疫抗原的循环CD4⁺T细胞、B细胞以及IgG和IgA抗体。