Imaoka K, Miller C J, Kubota M, McChesney M B, Lohman B, Yamamoto M, Fujihashi K, Someya K, Honda M, McGhee J R, Kiyono H
Immunobiology Vaccine Center, Department of Oral Biology, University of Alabama, Birmingham 35294, USA.
J Immunol. 1998 Dec 1;161(11):5952-8.
Female rhesus macaques were nasally immunized with p55gag (p55) of SIV and cholera toxin as a mucosal adjuvant. Nasal immunization induced Ag-specific IgA and IgG Abs in mucosal secretions (e.g., cervicovaginal secretions, rectal washes, and saliva) and serum. Furthermore, high numbers of p55-specific IgA and IgG Ab-forming cells were induced in mucosal effector sites, i.e., uterine cervix, intestinal lamina propria, and nasal passage. p55-specific CD4+ T cells in both systemic and mucosal compartments expressed IFN-gamma and IL-2 (Th1-type)- as well as IL-5, IL-6, and IL-10 (Th2-type)-specific mRNA. Moreover, p55-specific CTL activity was demonstrated in lymphocytes from blood, tonsils, and other lymphoid tissues. These results show that nasal immunization with SIV p55 with cholera toxin elicits both Th1- and selective Th2-type cytokine responses associated with the induction of SIV-specific mucosal and serum Abs, and CTL activity. These results offer a promise for the development of protective mucosal immunity to SIV.
将恒河猴雌性动物用猿猴免疫缺陷病毒(SIV)的p55gag(p55)和作为黏膜佐剂的霍乱毒素进行鼻腔免疫。鼻腔免疫可在黏膜分泌物(如宫颈阴道分泌物、直肠灌洗液和唾液)和血清中诱导产生抗原特异性IgA和IgG抗体。此外,在黏膜效应部位,即子宫颈、肠固有层和鼻道中诱导产生了大量p55特异性IgA和IgG抗体形成细胞。全身和黏膜区室中的p55特异性CD4 + T细胞表达γ干扰素和白细胞介素-2(Th1型)以及白细胞介素-5、白细胞介素-6和白细胞介素-10(Th2型)特异性mRNA。此外,在来自血液、扁桃体和其他淋巴组织的淋巴细胞中证实了p55特异性CTL活性。这些结果表明,用霍乱毒素进行SIV p55鼻腔免疫可引发与诱导SIV特异性黏膜和血清抗体以及CTL活性相关的Th1型和选择性Th2型细胞因子反应。这些结果为开发针对SIV的保护性黏膜免疫提供了希望。