Tauriainen Johanna, Gustafsson Karin, Göthlin Mårten, Gertow Jens, Buggert Marcus, Frisk Thomas W, Karlsson Annika C, Uhlin Michael, Önfelt Björn
Department of Laboratory Medicine, Division of Clinical Microbiology, Karolinska Institutet , Stockholm , Sweden.
Science for Life Laboratory, Department of Applied Physics, KTH Royal Institute of Technology , Stockholm , Sweden.
Front Immunol. 2015 Apr 28;6:196. doi: 10.3389/fimmu.2015.00196. eCollection 2015.
T cells are pivotal in the immune defense against cancers and infectious agents. To mount an effector response against cancer cells, T cells need to migrate to the cancer-site, engage in contacts with cancer cells, and perform their effector functions. Adoptive T cell therapy is an effective strategy as treatment of complications such as relapse or opportunistic infections after hematopoietic stem cell transplantations. This requires a sufficient amount of cells that are able to expand and respond to tumor or viral antigens. The cytokines interleukin (IL)-2 and IL-7 drive T cell differentiation, proliferation, and survival and are commonly used to expand T cells ex vivo. Here, we have used microchip-based live-cell imaging to follow the migration of individual T cells, their interactions with allogeneic monocytes, cell division, and apoptosis for extended periods of time; something that cannot be achieved by commonly used methods. Our data indicate that cells grown in IL-7 + IL-2 had similar migration and contact dynamics as cells grown in IL-2 alone. However, the addition of IL-7 decreased cell death creating a more viable cell population, which should be beneficial when preparing cells for immunotherapy.
T细胞在针对癌症和感染因子的免疫防御中起着关键作用。为了对癌细胞发起效应反应,T细胞需要迁移至癌症部位,与癌细胞接触,并发挥其效应功能。过继性T细胞疗法是治疗造血干细胞移植后复发或机会性感染等并发症的有效策略。这需要足够数量的能够扩增并对肿瘤或病毒抗原作出反应的细胞。细胞因子白细胞介素(IL)-2和IL-7驱动T细胞分化、增殖和存活,并且通常用于在体外扩增T细胞。在此,我们利用基于微芯片的活细胞成像技术长时间追踪单个T细胞的迁移、它们与异基因单核细胞的相互作用、细胞分裂和细胞凋亡;这是常用方法无法实现的。我们的数据表明,在IL-7 + IL-2中培养的细胞与仅在IL-2中培养的细胞具有相似的迁移和接触动态。然而,添加IL-7减少了细胞死亡,产生了更具活力的细胞群体,这在为免疫治疗制备细胞时应该是有益的。