Arens Ramon, Wang Peng, Sidney John, Loewendorf Andrea, Sette Alessandro, Schoenberger Stephen P, Peters Bjoern, Benedict Chris A
Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA.
J Immunol. 2008 May 15;180(10):6472-6. doi: 10.4049/jimmunol.180.10.6472.
CD4 T lymphocytes regulate the adaptive immune response to most viruses, both by providing help to CD8 T cells and B cells as well as through direct antiviral activity. Currently, no mouse cytomegalovirus (MCMV)-specific CD4 T cell responses are known. In this study, we identify and characterize 15 I-A(b)-restricted CD4 T cell responses specific for MCMV epitopes. CD4 T cells accumulate to high levels in the spleen and lungs during acute infection and produce multiple cytokines (IFN-gamma, TNF, IL-2, IL-10, and IL-17). Interestingly, IL-17 and IFN-gamma production within epitope-specific cells was found to be mutually exclusive. CD4 T cells recognizing a peptide derived from m09 were only detectable at later times of infection and displayed a unique cytokine production profile. In total, this study reveals that the MCMV-specific CD4 T cell response is complex and functionally diverse, highlighting its important role in controlling this persistent pathogen.
CD4 T淋巴细胞通过为CD8 T细胞和B细胞提供帮助以及直接的抗病毒活性，调节对大多数病毒的适应性免疫反应。目前，尚未发现针对小鼠巨细胞病毒（MCMV）的特异性CD4 T细胞反应。在本研究中，我们鉴定并表征了15种针对MCMV表位的I-A(b)限制性CD4 T细胞反应。在急性感染期间，CD4 T细胞在脾脏和肺中积累到高水平，并产生多种细胞因子（干扰素-γ、肿瘤坏死因子、白细胞介素-2、白细胞介素-10和白细胞介素-17）。有趣的是，发现表位特异性细胞内白细胞介素-17和干扰素-γ的产生相互排斥。识别源自m09的肽的CD4 T细胞仅在感染后期才可检测到，并表现出独特的细胞因子产生谱。总之，本研究揭示了MCMV特异性CD4 T细胞反应是复杂且功能多样的，突出了其在控制这种持续性病原体中的重要作用。
