Doyle A G, Ramm L, Kelso A
Queensland Institute of Medical Research, Post Office Royal Brisbane Hospital, Queensland, Australia.
Immunology. 1998 Mar;93(3):341-9. doi: 10.1046/j.1365-2567.1998.00404.x.
By virtue of their strong bias towards production of interferon-gamma (IFN-gamma), CD8+ T cells have the potential to promote the development of type 1 immune responses. We have previously shown that the CD4+ T-cell response to immunization with the protein antigen keyhole limpet haemocyanin (KLH) has a mixed interleukin-4 (IL-4)/IFN-gamma production profile. Here we show that this immunization regimen also stimulates accumulation in the draining lymph nodes of CD8+ T cells, which preferentially contain IFN-gamma mRNA ex vivo and secrete IFN-gamma protein in vitro. This provides a model to test whether CD8+ cell-derived IFN-gamma participates in the normal control of the immune response to a non-viable exogenous antigen. To investigate regulation of the anti-KLH response by the CD8+ population or IFN-gamma produced by this or other cell types, mice were administered depleting antibodies. Depletion of CD8+ cells had no effect on the frequency of clonogenic KLH-specific CD4+ T cells, the IL-4/IFN-gamma profiles of their progeny, or the isotype profiles of the serum antibody response to KLH. In contrast, IFN-gamma neutralization diminished cell accumulation in the lymph nodes and reduced both the frequency of KLH-specific CD4+ T cells that gave rise to IFN-gamma-producing clones and serum titres of KLH-specific IgG2a and IgG3. Therefore, despite the potential for cross-regulation, the CD4+ T-cell response to this immunogen is independent of the IFN-gamma-skewed CD8+ response.
由于CD8 + T细胞对干扰素-γ（IFN-γ）的产生具有强烈偏向性，它们有促进1型免疫反应发展的潜力。我们之前已经表明，CD4 + T细胞对钥孔血蓝蛋白（KLH）这种蛋白质抗原免疫的反应具有白细胞介素-4（IL-4）/IFN-γ混合产生模式。在此我们表明，这种免疫方案还能刺激CD8 + T细胞在引流淋巴结中的积累，这些细胞在体外优先含有IFN-γ mRNA并分泌IFN-γ蛋白。这提供了一个模型，用于测试CD8 +细胞衍生的IFN-γ是否参与对无活性外源性抗原免疫反应的正常调控。为了研究CD8 +群体或该群体或其他细胞类型产生的IFN-γ对KLH反应的调节作用，给小鼠注射了耗竭性抗体。耗尽CD8 +细胞对克隆形成的KLH特异性CD4 + T细胞的频率、其后代的IL-4/IFN-γ模式或对KLH血清抗体反应的同种型模式均无影响。相比之下，IFN-γ中和减少了淋巴结中的细胞积累，并降低了产生IFN-γ的克隆的KLH特异性CD4 + T细胞的频率以及KLH特异性IgG2a和IgG3的血清滴度。因此，尽管存在交叉调节的可能性，但CD4 + T细胞对这种免疫原的反应独立于IFN-γ偏向的CD8 +反应。
