Lo D, Freedman J, Hesse S, Palmiter R D, Brinster R L, Sherman L A
Department of Immunology, Scripps Research Institute, La Jolla, CA 92037.
Eur J Immunol. 1992 Apr;22(4):1013-22. doi: 10.1002/eji.1830220421.
To study the basis for immunological tolerance of peripheral tissue-specific antigens, a transgenic mouse line was established that expresses the influenza hemagglutinin (HA) on pancreatic islet beta cells (Ins-HA transgenic mice). When followed up to 14 months of age, Ins-HA transgenic mice did not develop spontaneous autoimmune disease. Upon immunization with HA-expressing viruses, high titers of HA-specific circulating antibody were detected; however, T cell responses by both the T helper and T cytolytic compartment were markedly reduced as compared with transgene-negative littermates, and no evidence could be found for islet infiltrates. Adoptive transfer of histocompatible lymphocytes from transgene-negative mice plus virus into irradiated Ins-HA hosts resulted in islet inflammation dominated by CD4+ T cells, indicating that the HA antigen was accessible to activated T cells. These results suggest that T cells can be rendered tolerant of antigens expressed outside the thymus.
为了研究外周组织特异性抗原免疫耐受的基础，构建了一种转基因小鼠品系，该品系在胰岛β细胞上表达流感血凝素（HA）（Ins-HA转基因小鼠）。对Ins-HA转基因小鼠随访至14月龄时，未发生自发性自身免疫性疾病。用表达HA的病毒免疫后，检测到高滴度的HA特异性循环抗体；然而，与转基因阴性同窝小鼠相比，T辅助细胞和T细胞溶解区室的T细胞反应均明显降低，且未发现胰岛浸润的证据。将转基因阴性小鼠的组织相容性淋巴细胞加病毒过继转移到受照射的Ins-HA宿主中，导致以CD4+T细胞为主的胰岛炎症，表明活化的T细胞能够接触到HA抗原。这些结果提示，T细胞可对外周表达的抗原产生耐受。
