Hagerty D T, Evavold B D, Allen P M
Department of Pathology, Washington University School of Medicine, St. Louis, MO 63110.
J Immunol. 1991 Nov 15;147(10):3282-8.
APC do not distinguish between self- and foreign proteins. Previous studies from our laboratory demonstrated that most endogenous host APC constitutively processed and presented the self-Ag, hemoglobin (Hb), as detected by the Hb-specific T cell hybridoma, YO1.6. We have now examined APC in organs known to be involved in RBC degradation (liver Kupffer cells and splenic small resting B cells) for the presence of Hb/Ia complexes and for the expression of the costimulation necessary to trigger proliferation of T cell clones. We detected Hb/Ia complexes not only on splenic small resting B cells, but also on liver Kupffer cells. Interestingly, complexes were not present on lymph node small resting B cells. Splenic small resting B cells expressed costimulatory activity and efficiently stimulated the Th2 clones only. The opposite pattern was observed with liver Kupffer cells, which expressed costimulatory activity for Th1 clones only. However, if costimulatory activity was provided for the Th2 clones (IL-1 beta) and Th1 clones (allogenic spleen cells), the clones did proliferate in response to Kupffer cells and small resting B cells, respectively. In this report we have demonstrated that 1) endogenously formed self Hb/Ia complexes are expressed on splenic small resting B cells and liver Kupffer cells but not on lymph node small resting B cells and 2) these APC are also able to limit the expression of costimulatory activity for Th2 and Th1 T cell clones. Thus, endogenous APC not only constitutively process and present the self-Ag Hb, but also limit expression of the costimulatory activity necessary to trigger T cell proliferation against a self-Ag. The constitutive processing and presentation of self-Ag, as well as the regulation of costimulatory activity on APC, is likely an important feature of the maintenance of self-tolerance.
抗原呈递细胞（APC）无法区分自身蛋白和外来蛋白。我们实验室之前的研究表明，大多数内源性宿主APC组成性地加工并呈递自身抗原血红蛋白（Hb），这可通过Hb特异性T细胞杂交瘤YO1.6检测到。我们现在检查了已知参与红细胞降解的器官中的APC（肝库普弗细胞和脾小静止B细胞），以检测Hb/Ia复合物的存在以及触发T细胞克隆增殖所需的共刺激分子的表达。我们不仅在脾小静止B细胞上检测到了Hb/Ia复合物，在肝库普弗细胞上也检测到了。有趣的是，淋巴结小静止B细胞上没有复合物。脾小静止B细胞表达共刺激活性，且仅能有效刺激Th2克隆。肝库普弗细胞则呈现相反的模式，其仅对Th1克隆表达共刺激活性。然而，如果为Th2克隆（白细胞介素-1β）和Th1克隆（同种异体脾细胞）提供共刺激活性，这些克隆会分别对库普弗细胞和小静止B细胞发生增殖反应。在本报告中，我们证明了：1）内源性形成的自身Hb/Ia复合物在脾小静止B细胞和肝库普弗细胞上表达，但不在淋巴结小静止B细胞上表达；2）这些APC也能够限制对Th2和Th1 T细胞克隆的共刺激活性的表达。因此，内源性APC不仅组成性地加工并呈递自身抗原Hb，还限制触发针对自身抗原的T细胞增殖所需的共刺激活性的表达。自身抗原的组成性加工和呈递以及APC上共刺激活性的调节，可能是维持自身耐受的一个重要特征。
