Creusot Rémi J, Biswas Jason S, Thomsen Lindy L, Tite John P, Mitchison N Avrion, Chain Benjamin M
Department of Immunology and Molecular Pathology, Windeyer Institute of Medical Sciences, University College London, GB.
Eur J Immunol. 2003 Jun;33(6):1686-96. doi: 10.1002/eji.200323811.
Cooperation between CD4(+) T cells can enhance the response and modulate the cytokine profile, and defining these parameters has become a major issue for multivalent-vaccine strategies. We explored cooperation using adoptive transfer of two populations of TCR transgenic T cells of different specificity. One was transferred without prior activation, whereas the second was activated for five days by antigen stimulation under polarizing culture conditions. Both populations were transferred into a single adoptive host and then primed by particle-mediated DNA delivery. Polarized Th1 cells (inducers) raised the frequency of IFN-gamma(+) cells within a naive (target) population, whereas Th2 inducers raised the frequency of IL-4(+) and reduced that of IL-2(+) cells. These effects were obtained when the genes for both antigens were on the same particle, favoring presentation by the same dendritic cell, but not when on different particles delivered to different dendritic cells. Autonomy of DC clusters allows linked sets of antigens (e.g. from a single pathogen) to maintain cytokine bias, but allows other independent responses, each with their own set of autonomous clusters.
CD4(+) T细胞之间的合作可以增强反应并调节细胞因子谱，确定这些参数已成为多价疫苗策略的一个主要问题。我们通过采用不同特异性的两群TCR转基因T细胞进行过继转移来探索合作。一群未经预先激活就进行转移，而另一群在极化培养条件下通过抗原刺激激活五天。两群细胞都转移到单个过继宿主中，然后通过颗粒介导的DNA递送进行致敏。极化的Th1细胞（诱导细胞）提高了幼稚（靶）群体中IFN-γ(+)细胞的频率，而Th2诱导细胞提高了IL-4(+)细胞的频率并降低了IL-2(+)细胞的频率。当两种抗原的基因在同一颗粒上时，有利于由同一树突状细胞呈递，可获得这些效应，但当在递送至不同树突状细胞的不同颗粒上时则不然。DC簇的自主性允许相连的抗原组（例如来自单个病原体的抗原）维持细胞因子偏向性，但允许其他独立反应，每个反应都有其自己的一组自主簇。
