dos Santos P V, Roffê E, Santiago H C, Torres R A, Marino A P, Paiva C N, Silva A A, Gazzinelli R T, Lannes-Vieira J
Laboratory of Autoimmunity and Immunoregulation, Department of Immunology, IOC-Fiocruz, Av. Brasil 4365, 21045-900, Rio de Janeiro, RJ, Brazil.
Microbes Infect. 2001 Oct;3(12):971-84. doi: 10.1016/s1286-4579(01)01461-7.
The determinants of the prevalence of CD8(+) T cells in the inflamed myocardium of Trypanosoma cruzi-infected patients and experimental animals are undefined. Using C3H/He mice infected with the Colombiana strain of T. cruzi, we found that the distribution of CD4(+)/CD8(-) and CD4(-)/CD8(+) T cells in the myocardium mirrors the frequency of cells expressing the CD62L(Low)LFA-1(High)VLA-4(High) activation phenotype among CD4(+)/CD8(-) and CD4(-)/CD8(+ )peripheral blood T cells. Consistently, vascular cell adhesion molecule-1-positive endothelial cells and a fine fibronectin network surrounding VLA-4(+) mononuclear cells were found in the inflamed myocardium. Further, interferon gamma (IFN-gamma) and IFN-gamma-induced chemokines (RANTES, MIG and CRG-2/IP-10), as well as JE/MCP-1 and MIP1-alpha, were found to be the dominant cytokines expressed in situ during acute and chronic myocarditis elicited by T. cruzi. In contrast, interleukin 4 mRNA was only detected during the chronic phase. Altogether, the results indicate that the distribution of T-cell subsets in the myocardium of T. cruzi-infected mice reflects the particular profile of adhesion molecules acquired by most peripheral CD8(+) T lymphocytes and point to the possibility that multiple IFN-gamma-inducible molecules present in the inflamed tissue contribute to the establishment and maintenance of T. cruzi-induced myocarditis.
克氏锥虫感染患者及实验动物炎症心肌中CD8(+) T细胞流行率的决定因素尚不明确。利用感染克氏锥虫哥伦比亚菌株的C3H/He小鼠,我们发现心肌中CD4(+)/CD8(-)和CD4(-)/CD8(+) T细胞的分布反映了CD4(+)/CD8(-)和CD4(-)/CD8(+)外周血T细胞中表达CD62L(Low)LFA-1(High)VLA-4(High)激活表型的细胞频率。一致地,在炎症心肌中发现血管细胞黏附分子-1阳性内皮细胞以及围绕VLA-4(+)单核细胞的精细纤连蛋白网络。此外,干扰素γ(IFN-γ)和IFN-γ诱导的趋化因子(RANTES、MIG和CRG-2/IP-10),以及JE/MCP-1和MIP1-α,被发现是克氏锥虫引发的急性和慢性心肌炎原位表达的主要细胞因子。相比之下,白细胞介素4 mRNA仅在慢性期检测到。总之,结果表明克氏锥虫感染小鼠心肌中T细胞亚群的分布反映了大多数外周CD8(+) T淋巴细胞获得的黏附分子的特定概况,并指出炎症组织中存在的多种IFN-γ诱导分子可能有助于克氏锥虫诱导的心肌炎的发生和维持。