腸病毒七十一型可在嬰幼兒造成致命的腦炎、肺水腫，甚至死亡，然而目前對其致病機轉之了解極其有限。臨床研究發現，腸病毒七十一型感染病患的中樞神經系統會有淋巴球浸潤的情形，這些浸潤的淋巴球分別為何及其功能現在還不清楚。我們的切片結果顯示，B、CD4+以及CD8+ T淋巴球皆會出現在病毒感染病患之腦部，為了研究這三種淋巴球在腸病毒七十一型感染時扮演的角色，我們使用了B、CD4+或CD8+ T淋巴球缺陷的小鼠。實驗結果發現，在低劑量腸病毒七十一型感染之後（1 x 107溶菌斑形成單位），野生型小鼠之存活率為75%，然而B淋巴球缺陷小鼠僅有6%存活，而且B淋巴球缺陷小鼠之中樞神經系統及周邊器官的病毒量也明顯高於野生型小鼠。在將抗腸病毒七十一型之抗體注射入B淋巴球缺陷小鼠後，其感染後之存活率高達100%，顯示B淋巴球製造的抗體可有效保護腸病毒七十一型感染之小鼠；然而在相同劑量的病毒感染下，CD4+或CD8+ T淋巴球缺陷小鼠的存活率及器官的病毒量與野生型小鼠卻是差不多的。另外，因為之前研究曾發現，CD4+ T淋巴球缺陷小鼠周邊的CD8+ T細胞數量會增加，因此我們移除野生鼠的CD4+ T淋巴球(CD4+ T-cell depletion)，當病毒感染後，其存活率與CD4+ T淋巴球缺陷鼠差不多，顯示並無其他免疫細胞對CD4+ T淋巴球之功能進行代償作用。當進ㄧ步使用較高病毒量（3 x 107溶菌斑形成單位）感染CD4+或CD8+ T淋巴球缺陷小鼠後，其存活率明顯比野生型小鼠降低許多，而且中樞神經系統及周邊器官中之病毒量也比野生型小鼠高出許多。因此，我們的實驗結果顯示，淋巴球在腸病毒七十一型感染時扮演保護的角色，而相較於CD4+或CD8+ T淋巴球而言，B淋巴球製造的抗體則扮演更重要的角色。

Enterovirus 71 (EV71) causes fatal encephalitis in infants and young children, but its pathogenesis remains unclear. Previous studies show that lymphocytes were present in the central nervous system of infected-patients. However, the types of lymphocytes have not been determined. Our autopsy data show that B, CD4+, and CD8+ T cells were all present in the central nervous system of an expired EV71-infected child. So we studied the roles of lymphocytes in EV71 infection using neonatal mice without B cells, CD4+ T cells, or CD8+ T cells. Our data show that only 6% of B cell deficient mice survived while the survival rate of wild-type mice was 75% after being infected with 1 x 107 plaque forming units of virus. The viral titers in the central nervous system and peripheral organs of B cell deficient mice were significantly higher than those of wild-type mice. After adoptive transfer of the anti-EV71 antibody, 100% of B cell deficient mice survived from EV71 infection with reduced viral titers in tissues, showing that the antibody produced by B cells protected mice against EV71 infection by reducing the viral loads in infected tissues. Under this condition, we were surprised to find that the survival rate of mice with CD4+ T cell or CD8+ T cell deficiency was comparable to that of wild-type mice after infection. The viral titers in the central nervous system and peripheral organs of them were also comparable to those of wild-type mice. Additional studies show that the survival rates of CD4+ T cell deficient mice and wild-type mice depleted with CD4+ T cells using the specific antibody were still comparable after infection, suggesting the compensation of CD4+ T-cell function by other immune cells is not likely. However, when CD4+ T cell and CD8+ T cell deficient mice were infected with a higher dose (3 x 107 plaque forming units) of virus, their survival rates were significantly lower than those of wild-type mice, and the viral titers in the central nervous system and peripheral organs of them were significantly higher than those of wild-type mice. Thus, our results show that lymphocytes protect mice from EV71 infection, and that antibody produced by B cells plays a more important role than CD4+ and CD8+ T cells.

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