Laidlaw Brian J, Zhang Nianzhi, Marshall Heather D, Staron Mathew M, Guan Tianxia, Hu Yinghong, Cauley Linda S, Craft Joe, Kaech Susan M
Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA; Department of Microbiology and Immunology, College of Veterinary Medicine, China Agricultural University, Beijing 100094, China.
Immunity. 2014 Oct 16;41(4):633-45. doi: 10.1016/j.immuni.2014.09.007. Epub 2014 Oct 9.
Tissue-resident memory T (Trm) cells provide enhanced protection against infection at mucosal sites. Here we found that CD4(+) T cells are important for the formation of functional lung-resident CD8(+) T cells after influenza virus infection. In the absence of CD4(+) T cells, CD8(+) T cells displayed reduced expression of CD103 (Itgae), were mislocalized away from airway epithelia, and demonstrated an impaired ability to recruit CD8(+) T cells to the lung airways upon heterosubtypic challenge. CD4(+) T cell-derived interferon-γ was necessary for generating lung-resident CD103(+) CD8(+) Trm cells. Furthermore, expression of the transcription factor T-bet was increased in "unhelped" lung Trm cells, and a reduction in T-bet rescued CD103 expression in the absence of CD4(+) T cell help. Thus, CD4(+) T cell-dependent signals are important to limit expression of T-bet and allow for the development of CD103(+) CD8(+) Trm cells in the lung airways following respiratory infection.
组织驻留记忆T（Trm）细胞可增强对黏膜部位感染的保护作用。在此，我们发现CD4(+) T细胞对于流感病毒感染后功能性肺驻留CD8(+) T细胞的形成至关重要。在缺乏CD4(+) T细胞的情况下，CD8(+) T细胞的CD103（整合素αEβ7）表达降低，定位偏离气道上皮，并且在异型亚型攻击时，向肺气道募集CD8(+) T细胞的能力受损。CD4(+) T细胞衍生的干扰素-γ是生成肺驻留CD103(+) CD8(+) Trm细胞所必需的。此外，转录因子T-bet在“未获得帮助”的肺Trm细胞中的表达增加，在缺乏CD4(+) T细胞帮助的情况下，T-bet表达的降低挽救了CD103的表达。因此，CD4(+) T细胞依赖性信号对于限制T-bet的表达并促进呼吸道感染后肺气道中CD103(+) CD8(+) Trm细胞的发育很重要。
