ROLE OF AUTOREACTIVE T CELLS IN MURINE AIDS

在小鼠获得性免疫缺陷综合征(MAIDS)中，一种动物模型， 在某些方面，对于艾滋病，C57BL/6小鼠感染了 亲生性和复制缺陷的小鼠白血病病毒株。这 感染导致淋巴样细胞快速增殖，导致 淋巴结病、脾肿大、高丙种球蛋白血症，随后是 严重的免疫抑制影响到细胞和体液的方方面面 豁免权。其发病机制(S)尚不清楚。 我们最近证明了大鼠CD4+自身反应性T细胞株和 克隆(AT)对同基因的B细胞具有特异性的增殖反应。 此外，当正常B细胞与tau照射的ATS共同培养时，B细胞 细胞增殖并分化为产生IgM/Ig G的细胞。 此外，将ATS注射到同基因宿主会导致脾肿大。 和高丙种球蛋白血症。此外，ATS还可以引发 幼稚的CD4+和CD8+T细胞，所产生的抗独特型细胞系是 指定的AAT。 因为在免疫效果上有明显的相似性 安非他明综合症和早期女佣和艾滋病，这项建议是针对 确定：(A)自身免疫和免疫抑制是否与 女佣是通过安非他明类兴奋剂的诱导来调解的-为了实现这一目标，我们 将决定女佣是否会增加B细胞反应性的频率 AT耗竭受照动物的ATS和IF重建 淋巴细胞将改变女佣的进程。此外，使用北线 印迹分析，我们将调查在保姆体内产生的CD4+T细胞， 像ATS一样，具有受限的T细胞受体异质性，以及(B)是否 AATS对ATS活性的调节--AATS对AT诱导的影响 B细胞体外增殖和分化的诱导 将进行体内脾肿大、高丙种球蛋白血症检测。 这些研究应该有助于更好地理解心绞痛的发病机制(S) 逆转录病毒诱导的自身免疫和免疫抑制。这将使 合理的艾滋病治疗方法。

In the murine acquired immunodeficiency syndrome (MAIDS), an animal model, in certain aspects, for AIDS, C57BL/6 mice are infected with a mixture of ecotropic and replication defective murine leukemia virus strains. This infection causes rapid proliferation of lymphoid cells leading to lymphadenopathy, splenomegaly, hypergammaglobulinemia, and followed by profound immunosuppression affecting all aspects of cellular and humoral immunity. The mechanism(s) of pathogenesis remains unclear. We have recently demonstrated that rat CD4+ auto-reactive T cell lines and clones (ATs) proliferate specifically in response to syngeneic B cells. Moreover, when normal B cells are cultured with tau-irradiated ATs, B cells proliferate and differentiate into IgM/IgG producing cells. Furthermore, injection of ATs into syngeneic hosts results in splenomegaly and hypergammaglobulinemia. Also, ATs can trigger the proliferation of naive CD4+ and CD8+ T cells, the resulting anti-idiotypic cell lines are designated AATs. Because there are clear similarities between the immunological effects of ATs and early stages of MAIDS and AIDS, this proposal is directed to determine: (a) whether autoimmunity and immunosuppression associated with MAIDS are mediated through the induction of ATs- To achieve this goal, we will determine whether MAIDS increases the frequency of B cell-reactive ATs and if reconstitution of irradiated animals with AT-depleted splenic lymphocytes will alter the course of MAIDS. In addition, using northern blot analysis, we will investigate whether CD4+ T cells, arising in MAIDS, like ATs, have a restricted T cell receptor heterogeneity, and (b) whether AATs regulate the activity of ATs- The effects of AATs on AT-induced proliferation and differentiation of B cells in vitro, induction of splenomegaly, and hypergammaglobulinemia in vivo will be tested. These studies should lead to a better understanding of the mechanism(s) of retrovirus-induced autoimmunity and immunosuppression. This will enable rational approaches for AIDS therapies.