Parronchi P, De Carli M, Manetti R, Simonelli C, Sampognaro S, Piccinni M P, Macchia D, Maggi E, Del Prete G, Romagnani S
Division of Clinical Immunology and Allergology, University of Florence, Italy.
J Immunol. 1992 Nov 1;149(9):2977-83.
The cytolytic potential of a total number of 118 CD4+ human T cell clones specific for purified protein derivative (PPD) from Mycobacterium tuberculosis, tetanus toxoid, Lolium perenne group I allergen (Lol p I), Poa pratensis group IX allergen (Poa p IX), or Toxocara canis excretory/secretory antigen(s) (TES) was assessed by both a lectin (PHA)-dependent and a MHC-restricted lytic assay and compared with their profile of cytokine secretion. The majority of clones with Th1 or Th0 cytokine profile exhibited cytolytic activity in both assays, whereas Th2 clones usually did not. There was an association between the cytolytic potential of T cell clones and their ability to produce IFN-gamma, even though IFN-gamma produced by T cell clones was not responsible for their cytolytic activity. IL-4 added in bulk culture before cloning inhibited not only the differentiation of PPD-specific T cells into Th1-like cell lines and clones, but also the development of their cytolytic potential. The depressive effect of IL-4 on the development of PPD-specific T cell lines with both Th1 cytokine profile and cytolytic potential was dependent on early addition of IL-4 in bulk cultures. In contrast, the addition in bulk culture of IFN-gamma enhanced both the cytolytic activity of PPD-specific T cell lines, as well as the proportion of PPD-specific T cell clones with cytolytic activity. The addition in bulk cultures before cloning of IFN-gamma or IFN-alpha favored the development of TES-specific and Poa p IX-specific T cells into T cell clones showing a Th0 or even a Th1, rather than a Th2, cytokine profile. Accordingly, most of TES- and Poa p IX-specific T cell clones derived from cultures containing IFN-gamma or IFN-alpha displayed strong cytolytic activity. These data indicate that the majority of human T cell clones that produce IFN-gamma, but not IL-4 (Th1-like), as well as of T cell clones that produce IFN-gamma in combination with IL-4 (Th0-like) are cytolytic. More importantly, they demonstrate that the addition of IFN (alpha and gamma) or IL-4 in bulk cultures before cloning may influence not only the cytokine profile of human CD4+ T cell clones but also their cytolytic potential.
通过凝集素（PHA）依赖性和MHC限制性裂解试验，评估了总共118个针对结核分枝杆菌纯化蛋白衍生物（PPD）、破伤风类毒素、黑麦草I组变应原（Lol p I）、早熟禾IX组变应原（Poa p IX）或犬弓首线虫排泄/分泌抗原（TES）的CD4 +人T细胞克隆的细胞溶解潜力，并将其与细胞因子分泌谱进行比较。大多数具有Th1或Th0细胞因子谱的克隆在两种试验中均表现出细胞溶解活性，而Th2克隆通常没有。T细胞克隆的细胞溶解潜力与其产生IFN-γ的能力之间存在关联，尽管T细胞克隆产生的IFN-γ与其细胞溶解活性无关。在克隆前大量培养中添加IL-4不仅抑制了PPD特异性T细胞向Th1样细胞系和克隆的分化，还抑制了其细胞溶解潜力的发展。IL-4对具有Th1细胞因子谱和细胞溶解潜力的PPD特异性T细胞系发展的抑制作用取决于在大量培养中早期添加IL-4。相反，在大量培养中添加IFN-γ增强了PPD特异性T细胞系的细胞溶解活性，以及具有细胞溶解活性的PPD特异性T细胞克隆的比例。在克隆前大量培养中添加IFN-γ或IFN-α有利于TES特异性和Poa p IX特异性T细胞发展为显示Th0甚至Th1而非Th2细胞因子谱的T细胞克隆。因此，大多数源自含有IFN-γ或IFN-α培养物的TES和Poa p IX特异性T细胞克隆表现出强大的细胞溶解活性。这些数据表明，大多数产生IFN-γ但不产生IL-4的人T细胞克隆（Th1样），以及与IL-4联合产生IFN-γ的T细胞克隆（Th0样）具有细胞溶解活性。更重要的是，它们表明在克隆前大量培养中添加IFN（α和γ）或IL-4不仅可能影响人CD4 + T细胞克隆的细胞因子谱，还可能影响其细胞溶解潜力。
