CD4 T-Cell-Mediated Heterologous Immunity between Mycobacteria and Poxviruses
CD4 T-Cell-Mediated Heterologous Immunity between Mycobacteria and Poxviruses
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DOI：
10.1128/jvi.02393-08
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发表时间：
2009-04-15
影响因子：
5.4
通讯作者：
Welsh, Raymond M.
中科院分区：
文献类型：
--
作者：
Mathurin, Keisha S.;Martens, Gregory W.;Welsh, Raymond M.
牛分枝杆菌的卡介苗（BCG）菌株在世界许多地方用作抗结核分枝杆菌的疫苗。一些流行病学证据表明，卡介苗免疫接种可能对其他病原体的抵抗力产生不可预测的影响。我们在这里显示，在小鼠模型中，BCG免疫接种，然后抗生素治疗，以清除宿主的病原体呈现三种小鼠品系部分抵抗感染牛痘病毒（VV），但不淋巴细胞性脉络丛脑膜炎病毒（LCMV）。VV攻击BCG免疫小鼠在感染后6天（p.i.）出现了显著的脾肿大和升高的CD 4和CD 8 T细胞应答。然而，早在感染后1至2天就可观察到对VV感染的抗性。并且在CD 4 T细胞群的抗体耗尽后丧失。BCG-而不是LCMV-免疫记忆表型CD 4 T细胞在VV攻击后优先产生γ干扰素（IFN-γ）。相反，LCMV免疫CD 8 T细胞在体内响应VV感染优先产生IFN-γ。在BCG免疫小鼠中，对VV感染的抵抗和VV诱导的CD 4 T细胞IFN-γ产生被环孢菌素A消除，环孢菌素A抑制通过T细胞受体的信号传导。因此，本研究证明了细菌和病毒之间的CD 4 T细胞介导的异源免疫。此外，它提出了一个问题，即人类接种卡介苗是否会改变对无关病原体的抵抗力。
The bacillus Calmette-Guerin ( BCG) strain of Mycobacterium bovis is used in many parts of the world as a vaccine against Mycobacterium tuberculosis. Some epidemiological evidence has suggested that BCG immunization may have unpredicted effects on resistance to other pathogens. We show here in a mouse model that BCG immunization followed by antibiotic treatment to clear the host of the pathogen rendered three strains of mice partially resistant to infection with vaccinia virus (VV) but not to lymphocytic choriomeningitis virus (LCMV). VV-challenged BCG-immune mice developed a striking splenomegaly and elevated CD4 and CD8 T-cell responses by 6 days postinfection (p.i.). However, resistance to VV infection could be seen as early as 1 to 2 days p.i. and was lost after antibody depletion of CD4 T-cell populations. BCG-but not LCMV-immune memory phenotype CD4 T cells preferentially produced gamma interferon (IFN-gamma) in vivo after VV challenge. In contrast, LCMV-immune CD8 T cells preferentially produced IFN-gamma in vivo in response to VV infection. In BCG-immune mice the resistance to VV infection and VV-induced CD4 T-cell IFN-gamma production were ablated by cyclosporine A, which inhibits signaling through the T-cell receptor. This study therefore demonstrates CD4 T-cell-mediated heterologous immunity between a bacterium and virus. Further, it poses the question of whether BCG immunization of humans alters resistance to unrelated pathogens.