Dynamic Motile T Cells Highly Respond to the T Cell Stimulation via PI3K-Akt and NF-kappa B Pathways

Abstract

T lymphocytes (T cells) circulate from the blood into secondary lymphoid organs for immune surveillance. In this study, we hypothesized that circulating T cells are heterogeneous and can be grouped according to their differential migratory capacity in response to chemoattractants, rather than expressions of certain receptors or cytokines. We further hypothesized that, at least in part, this intrinsic difference in motility may be related to the T cell function. We established motile (m-T) and non-motile T (nm-T) cell lines based on their response to the chemokine SDF-1 alpha. m-T cells showed more irregular and polarized morphologies than nm-T cells did. Interestingly, m-T cells produced higher levels of IL-2, a marker for T cell activation, than nm-T cells did after stimulation; however, no differences were observed in terms of surface expression of T cell receptors (TCR), adhesion molecules LFA-1 and ICAM-1, and chemokine receptor CXCR4. Both cell lines also showed similar membrane events (i.e., T cell-APC conjugation, LFA-1 accumulation at the immunological synapse, and TCR internalization). In contrast, PKC-theta, a downstream of PI3K-Akt pathway was constitutively activated in m-T cells and the activation was more prominent during T cell stimulation. Consequently, NF-kappa B activity was selectively upregulated in m-T cells. This study is the first, to our knowledge, to demonstrate that T cells can be subcategorized on the basis of their intrinsic migratory capacity in relation to T cell activation.