Vigorous innate and virus-specific cytotoxic T-lymphocyte responses to murine cytomegalovirus in the submaxillary salivary gland
Vigorous innate and virus-specific cytotoxic T-lymphocyte responses to murine cytomegalovirus in the submaxillary salivary gland
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DOI：
10.1128/jvi.77.3.1703-1717.2003
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发表时间：
2003-02-01
影响因子：
5.4
通讯作者：
Campbell, AE
中科院分区：
文献类型：
--
作者：
Cavanaugh, VJ;Deng, YP;Campbell, AE
为了更好地了解小鼠巨细胞病毒(MCMV)从唾液腺长期脱落的免疫学机制，对感染BALB/c小鼠的颌下腺(SMG)白细胞的表型和功能特征进行了分析。在感染后至少28天，由CD11c(+)主要组织相容性复合体11(+)CD11b(-)CD8α(+)树突状细胞和携带γ/Delta T细胞受体的CD3(+)T细胞组成的强健的先天免疫应答显著。同时，观察到泛NK(DX5(+))、CD3(+)和CD8(+)T细胞显著增加，而已知对病毒从该组织中清除至关重要的CD4(+)T细胞略有增加。SMG对MCWV感染的应答中，尤其是干扰素、白介素10和CC趋化因子的表达异常高。干扰素主要由CD4(+)、CD8(+)T细胞和DX5(+)CD3(+)T细胞产生。SMG CD8(+)T细胞在体外具有高度的细胞溶解能力，其中很大一部分细胞对免疫优势的MCMV多肽具有特异性。这些多肽特异性克隆并没有因高病毒滴度的存在而耗尽，尽管细胞介导的反应很强，但病毒滴度仍然在SMG中持续存在。相反，MCWV的复制可以有效地从引流的颈部和腺周淋巴结中清除，而这两个组织表现出的抗病毒反应要弱得多。我们的数据表明，由于颌下腺持续感染MCWV引起的粘膜炎症，可以激发、激活和保留强有力的先天和获得性免疫反应。
To better understand the immunological mechanisms that permit prolonged shedding of murine cytomegalovirus (MCMV) from the salivary gland, the phenotypic and functional characteristics of leukocytes infiltrating the submaxillary gland (SMG) were analyzed in infected BALB/c mice. A robust innate immune response, comprised of CD11c(+) major histocompatibility complex class 11(+) CD11b(-) CD8alpha(+) dendritic cells and gamma/delta T-cell receptor-bearing CD3(+) T cells was prominent through at least 28 days postinfection. Concurrently, a dramatic increase in pan-NK (DX5(+)) CD3(+) and CD8(+) T cells was observed, while CD4(+) T cells, known to be essential for viral clearance from this tissue, increased slightly. The expression particularly of gamma interferon but also of interleukin-10 and CC chemokines was extraordinarily high in the SMG in response to MCWV infection. The gamma interferon was produced primarily by CD4(+) and CD8(+) T lymphocytes and DX5(+) CD3(+) T cells. The SMG CD8(+) T cells were highly cytolytic ex vivo, and a significant proportion of these cells were specific to an immunodominant MCMV peptide. These peptide-specific clones were not exhausted by the presence of high virus titers, which persisted in the SMG despite the strength of the cell-mediated responses. In contrast, MCWV replication was efficiently cleared from the draining cervical and periglandular lymph nodes, a tissue displaying a substantially weaker antiviral response. Our data indicated that vigorous innate and acquired immune responses are elicited, activated, and retained in response to mucosal inflammation from persistent MCWV infection of the submaxillary gland.