Involvement of CD4+ Th1 cells in systemic immunity protective against primary and secondary challenges with Trypanosoma cruzi
Involvement of CD4+ Th1 cells in systemic immunity protective against primary and secondary challenges with Trypanosoma cruzi
复制标题
DOI：
10.1128/iai.68.1.197-204.2000
复制
发表时间：
2000-01-01
影响因子：
3.1
通讯作者：
Roodman, ST
中科院分区：
文献类型：
--
作者：
Hoft, DF;Schnapp, AR;Roodman, ST
一般来说，产生γ干扰素（ifn - γ）的CD4(+) Th1细胞对细胞内病原体的免疫控制很重要。我们之前证明了寄生虫特异性诱导ifn - γ反应与对细胞内原生动物克氏锥虫的抗性之间的关联。为了研究Th1反应与克氏锥虫抗性之间的潜在因果关系，我们研究了Th1细胞保护易感BALB/c小鼠免受毒性寄生虫攻击的能力。我们开发了能够在体内诱导极化Th1和Th2反应的免疫方案。诱导寄生虫特异性Th1反应，而不是Th2反应，可以保护BALB/c小鼠免受克氏t细胞的致命攻击。我们从BALB/c小鼠中获得了T. cruzi特异性CD4(+) Th1和Th2细胞系，这些细胞系被感染的巨噬细胞激活以产生相应的细胞因子反应谱。在克氏t细胞感染的巨噬细胞中，Th1细胞而非Th2细胞诱导一氧化氮的产生并抑制细胞内寄生虫的复制。尽管Th1细胞能够在体外抑制寄生虫的复制，但单独Th1细胞不能过继性地将抗克氏t型虫的保护转移到SCID小鼠身上。此外，尽管在我们的SCID小鼠模型中，CD4(+) T淋巴细胞的过继性转移被证明是对原发性克氏T病毒感染产生免疫保护的必要条件，但在缺乏CD4(+) T淋巴细胞的情况下，记忆免疫BALB/c小鼠的保护性次生效应功能可以转移到SCID小鼠身上。这些结果表明，尽管CD4(+) Th1细胞可以直接抑制细胞内寄生虫的复制，但这些细胞在克氏锥虫全身免疫中更重要的作用可能是为体内其他保护性效应功能的发展提供辅助活性。
In general, gamma interferon (IFN-gamma)-producing CD4(+) Th1 cells are important for the immunological control of intracellular pathogens. We previously demonstrated an association between parasite-specific induction of IFN-gamma responses and resistance to the intracellular protozoan Trypanosoma cruzi, To investigate a potential causal relationship between Th1 responses and T. cruzi resistance, we studied the ability of Th1 cells to protect susceptible BALB/c mice against virulent parasite challenges. We developed immunization protocols capable of inducing polarized Th1 and Th2 responses in vivo. Induction of parasite-specific Th1 responses, but not Th2 responses, protected BALB/c mice against virulent T. cruzi challenges. We generated T. cruzi-specific CD4(+) Th1 and Th2 cell lines from BALB/c mice that were activated by infected macrophages to produce their corresponding cytokine response profiles. Th1 cells, but not Th2 cells, induced nitric oxide production and inhibited intracellular parasite replication in T. cruzi-infected macrophages. Despite the ability to inhibit parasite replication in vitro, Th1 cells alone could not adoptively transfer protection against T. cruzi to SCID mice. In addition, despite the fact that the adoptive transfer of CD4(+) T lymphocytes was shown to be necessary for the development of immunity protective against primary T. cruzi infection in our SCID mouse model, protective secondary effector functions could be transferred to SCID mice from memory-immune BALB/c mice in the absence of CD4(+) T lymphocytes. These results indicate that, although CD4(+) Th1 cells can directly inhibit intracellular parasite replication, a more important role for these cells in T. cruzi systemic immunity may be to provide helper activity for the development of other effector functions protective in vivo.