Cukrowska B, Kozáková H, Reháková Z, Sinkora J, Tlaskalová-Hogenová H
Division of Immunology and Gnotobiology, Institute of Microbiology, Academy of Sciences of the Czech Republic, Prague.
Immunobiology. 2001 Dec;204(4):425-33. doi: 10.1078/0171-2985-00052.
Colonization of the gut with components of commensal microflora profoundly affects the development of the immune system. The aim of the present study was to investigate mucosal and systemic B cell responses during the first few days after intestinal association of colostrum-deprived piglets reared in germ-free (GF) conditions with non-pathogenic Escherichia coli O86. Specific intestinal anti-E. coli antibodies (Ab), among which IgA Ab prevailed, were found 4 days after colonization (72% of standard) and their amount decreased 11 days later reaching 22% of standard. In contrast to mucosal Ab, specific serum Ab remained at the level of GF animals at day 4 (less than 10% of standard) and markedly increased 15 days after colonization (156% of standard). In addition to the occurrence of specific Ab, increased amounts of total immunoglobulins (Ig) of all isotypes were detected in sera and intestinal washings. Using the ELISPOT method an increased number of IgM, IgG and IgA-secreting lymphocytes were found in spleen, mesenteric lymph nodes (MLN) and Peyer's patches (PP) in colonized animals as compared to GF piglets. Contrary to cells from these lymphatic organs, B cells from thymus were not affected by E. coli stimulation. Our results show that at the onset of intestinal colonization, non-pathogenic E. coli specifically and polyclonally stimulate the mucosal and systemic humoral immunity, but relatively soon after stimulation, mucosal-specific responses in gut decreases, indicating the possible beginning of inhibition mechanisms (oral tolerance).
共生微生物群落的成分在肠道内定殖会深刻影响免疫系统的发育。本研究的目的是调查在无菌(GF)条件下饲养的初乳缺乏仔猪与非致病性大肠杆菌O86肠道关联后的头几天内黏膜和全身B细胞反应。定殖后4天发现了特异性肠道抗大肠杆菌抗体(Ab),其中IgA抗体占主导,其含量为标准值的72%,11天后其含量下降,降至标准值的22%。与黏膜抗体不同,特异性血清抗体在第4天时仍处于GF动物的水平(低于标准值的10%),而定殖15天后显著增加(为标准值的156%)。除了出现特异性抗体外,在血清和肠道冲洗液中还检测到所有同种型的总免疫球蛋白(Ig)含量增加。使用ELISPOT方法发现,与GF仔猪相比,定殖动物的脾脏、肠系膜淋巴结(MLN)和派尔集合淋巴结(PP)中分泌IgM、IgG和IgA的淋巴细胞数量增加。与来自这些淋巴器官的细胞相反,胸腺中的B细胞不受大肠杆菌刺激的影响。我们的结果表明,在肠道定殖开始时,非致病性大肠杆菌特异性地、多克隆地刺激黏膜和全身体液免疫,但在刺激后相对不久,肠道中的黏膜特异性反应就会下降,这表明可能开始出现抑制机制(口服耐受)。