Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 24, Issue 4, Pages -Publisher
MDPI
DOI: 10.3390/ijms24043166
Keywords
cytotoxic CD8+T cells; neuron; cortical culture; acute brain slice; T cell-neuron co-culture; T cell migration; cytokine; inflammation; neurodegeneration; autoimmune disease
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Cytotoxic CD8+ T cells contribute to neuronal damage in inflammatory and degenerative CNS disorders, and their mechanism of cortical damage is not well understood. We developed in vitro and ex vivo models to study CD8+ T cell-neuron interactions. Our results show that under inflammatory conditions, T cells reduce migration velocity, change migratory patterns, and increase dwell time at neuronal soma and dendrites in response to added cytokines. These models provide promising platforms for studying neuron-immune cell interactions under inflammatory conditions.
Cytotoxic CD8+ T cells contribute to neuronal damage in inflammatory and degenerative CNS disorders, such as multiple sclerosis (MS). The mechanism of cortical damage associated with CD8+ T cells is not well understood. We developed in vitro cell culture and ex vivo brain slice co-culture models of brain inflammation to study CD8+ T cell-neuron interactions. To induce inflammation, we applied T cell conditioned media, which contains a variety of cytokines, during CD8+ T cell polyclonal activation. Release of IFN gamma and TNF alpha from co-cultures was verified by ELISA, confirming an inflammatory response. We also visualized the physical interactions between CD8+ T cells and cortical neurons using live-cell confocal imaging. The imaging revealed that T cells reduced their migration velocity and changed their migratory patterns under inflammatory conditions. CD8+ T cells increased their dwell time at neuronal soma and dendrites in response to added cytokines. These changes were seen in both the in vitro and ex vivo models. The results confirm that these in vitro and ex vivo models provide promising platforms for the study of the molecular details of neuron-immune cell interactions under inflammatory conditions, which allow high-resolution live microscopy and are readily amenable to experimental manipulation.
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