T CELL ABNORMALITIES IN AUTOIMMUNE 1PR/1PR MICE

描述（改编自申请人摘要）：MRL/Mp-lpr/lpr小鼠 发展成类似人类的系统性红斑狼疮（SLE）样疾病 SLE并发展为年龄依赖性淋巴组织增生性疾病， 异常T淋巴细胞亚群的大量聚集 的 异常的lpr T细胞对许多促有丝分裂刺激无反应。 表型正常的CD 4 + T细胞，仅占5%至10%， 在lpr小鼠淋巴细胞中， 自身免疫性疾病的发病机制。 这些携带CD 4的细胞可以识别 自身Ia抗原或与Ia结合的一些加工的自身肽。相互作用 这些自身反应性T细胞与B细胞的结合可能导致 自身抗体 因此，T细胞和自身抗原可能是导致 自身免疫性疾病。 T细胞杂交瘤通过以下方法产生： 将CD 4 + lpr T细胞与BW 5147融合。 这些杂交瘤将用于 研究自身反应性T细胞的T细胞受体库。 不 将细胞杂交瘤或其上清液与B细胞一起培养， 确定它们是否能激活B细胞产生抗体。 同种型 并测定产生的抗体的特异性。 B细胞来自 lpr小鼠可能具有一些内在特征， 刺激激活自身反应性T细胞。 虽然很明显 CD 4 + T细胞对淋巴细胞增殖的发展至关重要。 在lpr小鼠中，CD 4 + T细胞与异常T细胞之间的关系不明显。 清楚 CD 4 + T细胞可能是异常T细胞的前体细胞。 淋巴细胞浸润lpr小鼠的肾脏和唾液腺。 的 大部分浸润淋巴细胞是CD 4 + T细胞。 T细胞克隆 T细胞杂交瘤将由浸润的淋巴细胞产生 从LPR小鼠的肾脏和唾液腺获得。 T细胞 这些T细胞克隆和杂交瘤的受体（TCR）库将被 表征了 肾脏和唾液腺中的抗原呈递细胞 的lpr小鼠也将被分离，并且它们激活T细胞的能力将被检测。 确定克隆或杂交瘤。 这些研究将提供新的 深入了解自身反应性T细胞、异常T细胞 细胞和淋巴细胞浸润lpr小鼠的发炎器官。

DESCRIPTION (Adapted from the applicant's abstract): MRL/Mp-lpr/lpr mice develop a systemic lupus erythematosus (SLE) like disease similar to human SLE and develop an age dependent lymphoproliferative disease characterized by massive accumulation of an abnormal subset of T lymphocytes. The abnormal lpr T cells are unresponsive to many mitogenic stimuli. Phenotypically normal CD4+ T cells, which account for only 5 to 10 percent of the lymphocytes in lpr mice, also play an important role in the pathogenesis of autoimmune disease. These CD4 bearing cells may recognize self Ia antigens or some processed self peptides bound to Ia. Interaction of these autoreactive T cells with B cells may result in production of autoantibodies. T cells and self-antigens may, therefore, be the cause of autoimmune diseases in these mice. T cell hybridomas were generated by fusing CD4+ lpr T cells with BW5147. These hybridomas will be used to investigate the T cell receptor repertoire of the autoreactive T cells. T cell hybridomas or their supernatants will be cultured with B cells to determine if they can activate B cells to produce antibodies. The isotype and specificities of antibodies produced will be determined. B cells from lpr mice may possess some intrinsic features which render them more stimulatory in activating autoreactive T cells. While it is clear that CD4+ T cells are essential for the development of lymphoproliferation in lpr mice, the relationship between CD4+ T cells and abnormal T cells is not clear. CD4+ T cells may be the precursors of the abnormal T cells. Lymphocytes infiltrate the kidneys and salivary glands in lpr mice. The majority of the infiltrating lymphocytes are CD4+ T cells. T cell clones and T cell hybridomas will be generated from infiltrating lymphocytes obtained from the kidneys and salivary glands of lpr mice. The T cell receptor (TCR) repertoire of these T cell clones and hybridomas will be characterized. Antigen presenting cells in the kidneys and salivary glands of lpr mice will also be isolated and their ability to activate the T cell clones or hybridomas will be determined. These studies should provide new insights into the relationship between autoreactive T cells, abnormal T cells and lymphocytes infiltrating inflamed organs in lpr mice.