Oran Alp E, Robinson Harriet L
Emory Vaccine Center and Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
J Immunol. 2003 Aug 15;171(4):1999-2005. doi: 10.4049/jimmunol.171.4.1999.
DNA-based immunizations have been used to determine the patterns of type 1 and type 2 cytokines that can be induced in vivo for Ag-specific CD4(+) and CD8(+) T cells. IL-4 was used as a signature cytokine for a type 2 T cell response and IFN-gamma as the signature cytokine for a type 1 response. Gene gun deliveries of secreted Ags were used to bias responses toward type 2 and saline injections of cell-associated Ags to bias responses toward type 1. The studies revealed that gene gun bombardments of DNAs expressing secreted Ags strongly biased responses toward type 2, inducing IL-4-producing CD8(+) as well as CD4(+) T cells. Saline injections of DNAs expressing cell-associated Ags strongly biased responses toward type 1, inducing IFN-gamma-producing CD8(+) and CD4(+) cells. A mixed type 1/type 2 response of IFN-gamma-producing CD8(+) T cells and IL-4-producing CD4(+) T cells was found for gene gun deliveries of cell-associated Ags. Saline injections of secreted Ags raised a weakly type 1-biased response characterized by only slightly higher frequencies of IFN-gamma- than IL-4-producing CD4(+) and CD8(+) T cells. Studies in B cell knockout and hen egg lysozyme Ig transgenic mice revealed that B cells were required for the generation of IL-4-producing CD8(+) T cells.
基于DNA的免疫接种已被用于确定1型和2型细胞因子的模式，这些细胞因子可在体内针对抗原特异性CD4(+)和CD8(+)T细胞诱导产生。白细胞介素-4（IL-4）被用作2型T细胞反应的标志性细胞因子，而干扰素-γ（IFN-γ）被用作1型反应的标志性细胞因子。分泌性抗原的基因枪递送用于使反应偏向2型，而细胞相关抗原的生理盐水注射用于使反应偏向1型。研究表明，表达分泌性抗原的DNA的基因枪轰击强烈使反应偏向2型，诱导产生IL-4的CD8(+)以及CD4(+)T细胞。表达细胞相关抗原的DNA的生理盐水注射强烈使反应偏向1型，诱导产生IFN-γ的CD8(+)和CD4(+)细胞。对于细胞相关抗原的基因枪递送，发现产生IFN-γ的CD8(+)T细胞和产生IL-4的CD4(+)T细胞呈现1型/2型混合反应。分泌性抗原的生理盐水注射引发了一种弱1型偏向反应，其特征是产生IFN-γ的CD4(+)和CD8(+)T细胞的频率仅略高于产生IL-4的细胞。在B细胞敲除和鸡卵溶菌酶Ig转基因小鼠中的研究表明，B细胞是产生IL-4的CD8(+)T细胞生成所必需的。
