Cardillo F, Falcão R P, Rossi M A, Mengel J
Department of Immunology, Faculty of Medicine, University of São Paulo, Ribeirão Preto, Brazil.
Eur J Immunol. 1993 Oct;23(10):2597-605. doi: 10.1002/eji.1830231033.
In this work the suppressive activity of splenic T cells from young and aged BALB/c mice infected with Trypanosoma cruzi were compared and correlated with the development of autoimmune myocarditis. The T cells from young adult BALB/c mice with acute T. cruzi infection exhibit suppressor activity when added to full allogeneic or Mls-disparate mixed lymphocyte cultures. This suppression could not be reverted by exogenous interleukin (IL)-2 and was not directly dependent on the presence of IL-4, IL-10 or transforming growth factor-beta. Further characterization of the T cell lineage responsible for the suppressor activity by in vitro and/or in vivo depletion with monoclonal antibody to alpha beta or gamma delta T cell receptor revealed that splenic gamma delta T cells function as suppressor lymphocytes in young T. cruzi-infected mice. In addition, these young adult BALB/c mice do not develop autoimmune myocarditis and showed a low incidence of syngeneic heart graft rejection in the early chronic phase of the infection. In contrast, T cells from acutely infected aged BALB/c mice lacked demonstrable T suppressor activity. Furthermore, these mice developed a severe autoimmune myocarditis as early as 2 months after the onset of the infection, when the majority of them reject syngeneic heart grafts. These findings suggest that a gamma delta T cell-mediated suppressor mechanism may operate in the avoidance of the breaking of tissue-specific tolerance during the acute infection. Moreover, such a mechanism is likely related to the immune system chronobiology.
在本研究中，对感染克氏锥虫的年轻和老年BALB/c小鼠脾脏T细胞的抑制活性进行了比较，并将其与自身免疫性心肌炎的发展相关联。急性感染克氏锥虫的年轻成年BALB/c小鼠的T细胞在加入完全异基因或Mls不匹配的混合淋巴细胞培养物时表现出抑制活性。这种抑制不能被外源性白细胞介素（IL）-2逆转，也不直接依赖于IL-4、IL-10或转化生长因子-β的存在。通过用抗αβ或γδT细胞受体的单克隆抗体进行体外和/或体内清除来进一步表征负责抑制活性的T细胞谱系，结果显示脾脏γδT细胞在年轻的感染克氏锥虫的小鼠中作为抑制性淋巴细胞发挥作用。此外，这些年轻成年BALB/c小鼠不会发生自身免疫性心肌炎，并且在感染的早期慢性阶段同种异体心脏移植排斥的发生率较低。相比之下，急性感染的老年BALB/c小鼠的T细胞缺乏可证明的T抑制活性。此外，这些小鼠在感染开始后2个月就发展出严重的自身免疫性心肌炎，此时它们中的大多数排斥同种异体心脏移植。这些发现表明，γδT细胞介导的抑制机制可能在急性感染期间避免组织特异性耐受性的破坏中起作用。此外，这种机制可能与免疫系统的生物钟学有关。
