Joint Clinical Research Center, Kampala, Uganda.
Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
J Clin Invest. 2018 Jul 2;128(7):2763-2773. doi: 10.1172/JCI97377. Epub 2018 May 21.
Vaccine responses vary by geographic location. We have previously described how HIV-associated inflammation leads to fibrosis of secondary lymph nodes (LNs) and T cell depletion. We hypothesized that other infections may cause LN inflammation and fibrosis, in a process similar to that seen in HIV infection, which may lead to T cell depletion and affect vaccine responses. We studied LNs of individuals from Kampala, Uganda, before and after yellow fever vaccination (YFV) and found fibrosis in LNs that was similar to that seen in HIV infection. We found blunted antibody responses to YFV that correlated to the amount of LN fibrosis and loss of T cells, including T follicular helper cells. These data suggest that LN fibrosis is not limited to HIV infection and may be associated with impaired immunologic responses to vaccines. This may have an impact on vaccine development, especially for infectious diseases prevalent in the developing world.
疫苗反应因地理位置而异。我们之前描述了 HIV 相关炎症如何导致次级淋巴结 (LN) 和 T 细胞耗竭的纤维化。我们假设其他感染可能导致 LN 炎症和纤维化,这一过程类似于 HIV 感染,可能导致 T 细胞耗竭并影响疫苗反应。我们研究了乌干达坎帕拉的个体在接种黄热病疫苗 (YFV) 前后的淋巴结,发现淋巴结纤维化类似于 HIV 感染。我们发现 YFV 抗体反应减弱,与 LN 纤维化和 T 细胞(包括滤泡辅助 T 细胞)耗竭的程度相关。这些数据表明 LN 纤维化不仅限于 HIV 感染,可能与对疫苗的免疫反应受损有关。这可能对疫苗开发产生影响,尤其是对发展中国家流行的传染病。