Mendes-da-Cruz Daniella Arêas, de Meis Juliana, Cotta-de-Almeida Vinícius, Savino Wilson
Department of Immunology, Oswaldo Cruz Institute, Manguinhos, 21045-900 Rio de Janeiro, Brazil.
Microbes Infect. 2003 Aug;5(10):825-32. doi: 10.1016/s1286-4579(03)00156-4.
We investigated the thymic and peripheral T-lymphocyte subsets in BALB/c mice undergoing acute or chronic Trypanosoma cruzi infection, in terms of expression of particular Vbeta rearrangements of the T-cell receptor. We first confirmed the severe depletion of CD4(+)CD8(+) thymocytes following acute T. cruzi infection. By contrast, the numbers of CD4(+)CD8(+) cells in subcutaneous lymph nodes increased up to 16 times. In subcutaneous lymph nodes, we found CD4(+)CD8(+) cells that expressed prohibited segments TCRVbeta5 and TCRVbeta12 (which are physiologically deleted in the thymus of BALB/c mice), as did some mature single-positive cells (CD4(+)CD8(-) and CD4(-)CD8(+)). In the thymus of infected animals, although higher numbers of immature cells bearing such Vbeta segments were seen, they were no longer detected in the mature single-positive stage, suggesting that negative selection occurs normally. We also found increased numbers of cells bearing the potentially autoreactive phenotype TCRVbeta5(+) and TCRVbeta12(+) in T-lymphocyte subsets from subcutaneous lymph nodes of T. cruzi chronically infected mice. In conclusion, our data indicate that immature T lymphocytes bearing prohibited TCRVbeta segments leave the thymus and gain the lymph nodes, where they further differentiate into mature CD4(+) or CD8(+) cells. Conjointly, these findings show changes in the shaping of the central and peripheral T-cell repertoire in both acute and chronic phases of murine T. cruzi infection. The release of potentially autoreactive T cells in the periphery of the immune system may contribute to the autoimmune process found in both murine and human Chagas' disease.
我们根据T细胞受体特定Vβ重排的表达情况，研究了急性或慢性克氏锥虫感染的BALB/c小鼠的胸腺和外周T淋巴细胞亚群。我们首先证实了急性克氏锥虫感染后CD4(+)CD8(+)胸腺细胞的严重耗竭。相比之下，皮下淋巴结中CD4(+)CD8(+)细胞的数量增加了16倍。在皮下淋巴结中，我们发现了表达禁止片段TCRVβ5和TCRVβ12（在BALB/c小鼠胸腺中生理性缺失）的CD4(+)CD8(+)细胞，一些成熟的单阳性细胞（CD4(+)CD8(-)和CD4(-)CD8(+)）也表达。在感染动物的胸腺中，虽然可见更多携带此类Vβ片段的未成熟细胞，但在成熟单阳性阶段不再检测到它们，这表明阴性选择正常发生。我们还发现，在慢性感染克氏锥虫的小鼠皮下淋巴结的T淋巴细胞亚群中，携带潜在自身反应性表型TCRVβ5(+)和TCRVβ12(+)的细胞数量增加。总之，我们的数据表明，携带禁止的TCRVβ片段的未成熟T淋巴细胞离开胸腺并进入淋巴结，在那里它们进一步分化为成熟的CD4(+)或CD8(+)细胞。同时，这些发现显示了小鼠克氏锥虫感染急性期和慢性期中央和外周T细胞库形成的变化。免疫系统外周潜在自身反应性T细胞的释放可能导致小鼠和人类恰加斯病中发现的自身免疫过程。
