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

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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