Abstract
BackgroundHuman T cells play an important role in pathogen clearance, but their aberrant activation is also linked to numerous diseases. T cells are activated by the concurrent induction of the T cell receptor (TCR) and one or more costimulatory receptors. The characterization of signaling pathways induced by TCR and/or costimulatory receptor activation is critical, since these pathways are excellent targets for novel therapies for human disease. Although studies using human T cell lines have provided substantial insight into these signaling pathways, no comprehensive, direct comparison of these cell lines to activated peripheral blood T cells (APBTs) has been performed to validate their usefulness as a model of primary T cells.Methodology/Principal FindingsWe used quantitative biochemical techniques to compare the activation of two widely used human T cell lines, Jurkat E6.1 and HuT78 T cells, to APBTs. We found that HuT78 cells were similar to APBTs in proximal TCR-mediated signaling events. In contrast, Jurkat E6.1 cells had significantly increased site-specific phosphorylation of Pyk2, PLCγ1, Vav1, and Erk1/Erk2 and substantially more Ca2+ flux compared to HuT78 cells and APBTs. In part, these effects appear to be due to an overexpression of Itk in Jurkat E6.1 cells compared to HuT78 cells and APBTs. Both cell lines differ from APBTs in the expression and function of costimulatory receptors and in the range of cytokines and chemokines released upon TCR and costimulatory receptor activation.Conclusions/SignificanceBoth Jurkat E6.1 and HuT78 T cells had distinct similarities and differences compared to APBTs. Both cell lines have advantages and disadvantages, which must be taken into account when choosing them as a model T cell line.
Highlights
Human T cells control the extent and focus of the adaptive immune response to pathogens
In order to compare proximal T cell receptor (TCR)-mediated signaling events in Jurkat E6.1 T cells, HuT78 T cells, and activated peripheral blood T cells (APBTs), equal cell numbers were activated with maximal doses of stimulatory TCR antibodies
Due to its importance in downstream T cell functions, we examined whether the hyperphosphorylation of PLC-c1 in Jurkat E6.1 T cells lead to alterations in the levels of TCR-induced Ca2+ influx in the T cell lines and APBTs
Summary
Human T cells control the extent and focus of the adaptive immune response to pathogens. Costimulation is critical for the specificity of the immune response because it allows T cells to be activated only during acute infection. This enables the adaptive immune system to mount a response to foreign invaders while tolerating its own cells. Signaling pathways that are activated by TCR and/or costimulatory receptors are good targets for the development of therapies to these diseases [4,5]. Human T cells play an important role in pathogen clearance, but their aberrant activation is linked to numerous diseases. The characterization of signaling pathways induced by TCR and/or costimulatory receptor activation is critical, since these pathways are excellent targets for novel therapies for human disease. Studies using human T cell lines have provided substantial insight into these signaling pathways, no comprehensive, direct comparison of these cell lines to activated peripheral blood T cells (APBTs) has been performed to validate their usefulness as a model of primary T cells
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