Protective role of gamma interferon during the recall response to influenza virus
Protective role of gamma interferon during the recall response to influenza virus
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DOI：
10.1128/jvi.72.8.6637-6645.1998
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发表时间：
1998-08-01
影响因子：
5.4
通讯作者：
Bona, CA
中科院分区：
文献类型：
--
作者：
Bot, A;Bot, S;Bona, CA
在对流感病毒的二次免疫应答期间，病毒特异性T记忆细胞是γ干扰素（IFN-γ）的主要来源。我们评估了IFN-γ对野生型小鼠和先前用A/HK/68（H3 N2）病毒免疫的IFN-γ-/-小鼠针对A/WSN/33（H1N1）病毒的异源保护的贡献。在接受不同剂量的A/WSN/33病毒攻击后，IFN-gamma-/-小鼠的存活率显着降低。这与IFN-γ-/-小鼠在攻击后第7天完全清除肺部病毒的能力受损有关，尽管注意到病毒滴度显著降低。然而，IFN-γ-/-小鼠产生了与野生型小鼠相似的A型流感病毒交叉反应性细胞毒性T淋巴细胞（CTL），如细胞毒性和用于估计CTL前体频率的有限稀释测定所证明的。IFN-γ-/-小鼠中T细胞的肺部募集没有受到显著影响，CD 4（+）和CD 8（+）T细胞的百分比与野生型小鼠相似。来自IFN-γ-/-小鼠的T细胞没有显示出向Th 2分布的显著转变。此外，IFN-γ-/-小鼠保留了产生显著滴度的WSN和HK病毒特异性血凝抑制抗体的能力。总之，这些结果与IFN-γ在针对流感病毒的异源应答期间的保护作用一致，其独立于交叉反应性CTL的产生和局部募集。
During secondary immune responses to influenza virus, virus-specific T memory cells are a major source of gamma interferon (IFN-gamma). We assessed the contribution of IFN-gamma to heterologous protection against the A/WSN/33 (H1N1) virus of wild-type and IFN-gamma-/- mice previously immunized with the A/HK/68 (H3N2) virus. The IFN-gamma-/- mice displayed significantly reduced survival rates subsequent to a challenge with various doses of the A/WSN/33 virus. This was associated with an impaired ability of the IFN-gamma-/- mice to completely clear the pulmonary virus by day 7 after the challenge, although significant reduction of the virus titers was noted. However, the IFN-gamma-/- mice developed type A influenza virus cross-reactive cytotoxic T lymphocytes (CTLs) similar to the wild-type mice, as demonstrated by both cytotoxicity and a limiting-dilution assay for the estimation of CTL precursor frequency. The pulmonary recruitment of T cells in IFN-gamma-/- mice was not dramatically affected, and the percentage of CD4(+) and CD8(+) T cells was similar to that of wild-type mice. The T cells from IFN-gamma-/- mice did not display a significant switch toward a Th2 profile. Furthermore, the IFN-gamma-/- mice retained the ability to mount significant titers of WSN and HK virus-specific hemagglutination-inhibiting antibodies. Together, these results are consistent with a protective role of IFN-gamma during the heterologous response against influenza virus independently of the generation and local recruitment of crossreactive CTLs.