A transfer study of human tonsillar lymphocytes into NOD/LtSz-scid/scid mice

如之前对动物和人类的大量研究所示，鼻咽粘膜衬里中提供了复杂的共同粘膜免疫系统。归巢理论已被确定用于解释致敏淋巴细胞从诱导部位向不同远处粘膜部位的募集。然而，这些前体细胞B和T细胞如何募集到远处粘膜部位以及最终产生效应抗体的B细胞如何分化并进行克隆扩增仍有待研究。为了挑战这个问题，我们已经做了一个人扁桃体淋巴细胞到NOD/LtSz-scid/scid小鼠的转移研究，并获得了成功的结果，其中人白细胞移植在脾脏和其他非淋巴器官，如肺和肝。在流式细胞术分析中，在人扁桃体单核细胞移植后4周，在NOD/LtSz-scid/scid小鼠脾脏中检测到不同程度的人辅助/诱导和抑制/细胞毒性T细胞。 ...更多信息 重新腹膜内接种到小鼠中。然而，在CB-17酸性小鼠中没有人扁桃体细胞的植入。免疫组化研究显示，人白细胞存在于脾，胸腺，肺，肝，但不是在正常的鼻咽或tubotympanal粘膜。从携带β链球菌的患者中获得人扁桃体淋巴细胞移植于NOD-酸性小鼠，在这些小鼠的血清中检测到M-蛋白特异性人IgG和伊加抗体活性。经鼻内免疫的M-蛋白和霍乱毒素，这些小鼠，M-蛋白特异性的人伊加抗体滴度在鼻洗液中高于那些没有鼻内攻击的M-蛋白的小鼠。在免疫染色研究中，将人T和B细胞募集到具有较高M蛋白特异性人伊加抗体滴度的小鼠的鼻咽淋巴网状组织周围的鼻粘膜。这些结果可能使我们能够使用这个模型作为一个有前途的工具，用于评估淋巴细胞归巢和招募前体淋巴细胞的最终分化机制，用于在外周粘膜部位（如鼻咽和咽鼓管）进行抗原特异性免疫应答。少

A sophisticated common mucosal immunity system is provided in the nasopharyngeal mucosal linings, as previously shown by a large number of studies on animals and humans. Homing theory is now settled down for explaining recruitments of primed lymphocytes from inductive site to various distant mucosal sites. However, it still remains to be investigated how these precursor cell B and T cells recruit to the distant mucosal sites and how final effector antibody-producing B cells differentiate and conduct a clonal expansion. To challenge this issue, we have done a transfer study of human tonsillar lymphocytes into NOD/LtSz-scid/scid mice and obtained successful results in which human leukocytes are engrafted in the spleens and other non-lymphoid organs such as lung and liver. In a flow cytometric analysis, human helper/inducer and suppressor/cytotoxic T cells were detected in various degrees in spleens of NOD/LtSz-scid/scid mice at a 4-week interval after human tonsillar mononuclear cells we … More re inoculated intraperitoneally into the mice. However, there was no engraftment of human tonsillar cells in CB-17 acid mice. An immunohistochemical study revealed that human leukocytes were present in the spleen, thymus, lung, and liver, but not in normal nasopharyngeal or tubotympanal mucosae. In NOD-acid mice engrafted with human tonsillar lymphocytes obtained from patients carrying β Streptococcus, M-protein specific human IgG and IgA antibody activities were detected in the sera of these mice. Upon an intranasal immunization of M-protein and cholera toxin to these mice, M-protein specific human IgA antibody titers in nasal washings were higher than those of mice without intranasal challenge of M-proteins. In an immunostaining study, human T and B cells were recruited to the nasal mucosae around the nasopharyngeal lymphoreticular tissue of those mice having higher M-protein specific human IgA antibody titers. These results may allow us to use this model as a promising tool for evaluating the lymphocyte homing and mechanism of the final differentiation of recruiting precursor lymphocytes for mounting antigen-specific immune response in peripheral mucosal, sites such as the nasopharynx and tubotympanum. Less