Department of Microbiology and Immunology, College of Medicine, University of Saskatchewan, Saskatchewan, Canada.
Int Immunol. 2009 Nov;21(11):1213-24. doi: 10.1093/intimm/dxp085. Epub 2009 Sep 7.
We address here the role of CD4 T cell cooperation in the activation of CD4 T cells. Administration of aggregated hen egg lysozyme (HEL) without microbial adjuvant to BALB/c mice normally generates cytokine-producing CD4 T cells specific for the HEL major peptide, HEL(105-120), as well as CD4 T cells specific for HEL non-major peptides. The prior administration of HEL(105-120) ablates the generation of cytokine-secreting CD4 T cells specific for HEL(105-120), as well as the CD4 T cells specific for HEL non-major peptides, normally generated upon HEL challenge. Thus, the activation of HEL non-major peptide-specific CD4 T cells appears to depend upon the HEL(105-120)-specific CD4 T cell population. In contrast, when HEL(105-120) and saline-treated mice are challenged with HEL coupled to ovalbumin (OVA), CD4 T cell responses to HEL non-major peptides and to OVA are the same, whereas treated mice still do not generate cytokine-secreting cells specific for HEL(105-120). We infer that the administration of HEL(105-120) does not generate regulatory cells capable of down-regulating CD4 T cell responses to HEL and OVA peptides. OVA-specific CD4 T cells restore the generation of HEL non-major peptide-specific T cells in the absence of HEL major peptide-specific T cells. We conclude that the generation of CD4 T cells producing IL-2, IFN-gamma and IL-4 requires CD4 T cell cooperation and that this cooperation is not mediated simply by CD40-CD40L interactions. We also conclude from these observations that there is no requirement for a microbial or danger signal for CD4 T cell activation.
我们在这里探讨 CD4 T 细胞协同作用在 CD4 T 细胞激活中的作用。向 BALB/c 小鼠施用未用微生物佐剂聚集的鸡卵溶菌酶（HEL）通常会产生针对 HEL 主要肽段 HEL（105-120）的细胞因子产生 CD4 T 细胞，以及针对 HEL 非主要肽段的 CD4 T 细胞。预先给予 HEL（105-120）可消除针对 HEL（105-120）的细胞因子分泌 CD4 T 细胞以及通常在 HEL 挑战时产生的针对 HEL 非主要肽段的 CD4 T 细胞的生成。因此，HEL 非主要肽特异性 CD4 T 细胞的激活似乎依赖于 HEL（105-120）特异性 CD4 T 细胞群体。相反，当用 HEL 与卵清蛋白（OVA）偶联物挑战 HEL（105-120）和盐水处理的小鼠时，对 HEL 非主要肽段和 OVA 的 CD4 T 细胞反应是相同的，而处理过的小鼠仍未产生针对 HEL（105-120）的细胞因子分泌细胞。我们推断，给予 HEL（105-120）不会产生能够下调针对 HEL 和 OVA 肽的 CD4 T 细胞反应的调节性细胞。OVA 特异性 CD4 T 细胞在缺乏 HEL 主要肽特异性 T 细胞的情况下恢复 HEL 非主要肽特异性 T 细胞的生成。我们得出的结论是，产生产生 IL-2、IFN-γ和 IL-4 的 CD4 T 细胞需要 CD4 T 细胞协同作用，并且这种协同作用不是通过 CD40-CD40L 相互作用介导的。我们还从这些观察结果中得出结论，CD4 T 细胞的激活不需要微生物或危险信号。
