Induction of common mucosal immunity by hormonally immunomodulated peripheral immunization
Induction of common mucosal immunity by hormonally immunomodulated peripheral immunization
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DOI：
10.1128/iai.64.4.1100-1109.1996
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发表时间：
1996-04-01
影响因子：
3.1
通讯作者：
Araneo, BA
中科院分区：
文献类型：
--
作者：
Daynes, RA;Enioutina, EY;Araneo, BA
本报告中描述的研究表明，如果改变微环境条件以模拟粘膜相关淋巴组织中正常存在的微环境条件（例如，Peyer’s patches）。发现原位暴露于激素1 α，25-二羟基维生素D-3的免疫调节影响的淋巴结淋巴细胞产生的γ干扰素和白细胞介素-2（IL-2）较少，而IL-4、IL-5和IL-10远多于对照动物的淋巴细胞。当与B型肝炎表面抗原（HBsAg）疫苗接种相结合时，从外周淋巴结表型到派尔斑样模式的免疫调节转换促进了全身和共同粘膜免疫应答的诱导。这是通过观察到血清抗HBsAg抗体浓度增加以及发现仅在经牛磺酸处理的动物的泌尿生殖道、泪腺、粪便和口腔分泌物中可检测到抗HBsAg分泌性抗体来确定的。此外，在接种疫苗后，在经疫苗处理的动物的肺和小肠的固有层中可检测到特异性抗体分泌细胞，表明抗原特异性B细胞的归巢特性受到处理程序的影响。25-二羟基维生素D-3和脱氢表雄酮一起用作激素免疫调节剂。这种新的免疫技术可能为有效干预性传播疾病和其他由粘膜病原体引起的疾病提供新的机会。
The study described in this report demonstrates that peripheral lymph nodes draining nonmucosal tissues can effectively serve as induction sites for the establishment of common mucosal immunity if the microenvironmental conditions are altered to mimic those normally present within mucosa-associated lymphoid tissues (e.g., Peyer's patches). Lymph node lymphocytes exposed in situ to the immunomodulatory influences of the hormone 1 alpha,25-dihydroxy vitamin D-3 were found to produce less gamma interferon and interleukin-2 (IL-2) and far more IL-4, IL-5, and IL-10 than lymphocytes from control animals. When coupled with vaccination with hepatitis B surface antigen (HBsAg), the hormone-immunomodulated switch from a peripheral lymph node phenotype to a Peyer's patch-like pattern promoted the induction of both a systemic and a common mucosal immune response. This was deter mined by the observed increased concentrations of serum anti-HBsAg antibody and by finding that anti-HBsAg secretory antibodies were detectable in urogenital, lachrymal, fecal, and oral secretions only in the hormone-treated animals. In addition, specific antibody-secreting cells were detectable in the lamina propria of the lungs and small intestines of the hormone-treated animals subsequent to vaccination, indicating that the homing properties of antigen-specific B cells were being affected by the treatment procedure, The humoral and mucosal immune responses were further augmented if both 1 alpha,25-dihydroxy vitamin D-3 and dehydroepiandrosterone were used together as hormonal immunomodulators. This novel immunization technique may afford new opportunities to effectively intervene in sexually transmitted diseases and other diseases caused by mucosal pathogens.