One of the potential mechanisms of peripheral tolerance is the unresponsiveness of T cells to secondary antigenic stimulation as a result of the induction of anergy. It has been widely reported that antigenic unresponsiveness may be due to uncoupling of MAPK signal transduction pathways. However, such signaling defects in anergic T cell populations have been mainly identified using immortalized T cell lines or T cell clones, which do not truly represent primary Ag-specific T cells. We have therefore attempted to quantify signaling events in murine primary Ag-specific T cells on an individual cell basis, using laser-scanning cytometry. We show that there are marked differences in the amplitude and cellular localization of phosphorylated ERK p42/p44 (ERK1/2) signals when naive, primed and anergic T cells are challenged with peptide-pulsed dendritic cells. Primed T cells display more rapid kinetics of phosphorylation and activation of ERK than naive T cells, whereas anergic T cells display a reduced ability to activate ERK1/2 upon challenge. In addition, the low levels of pERK found in anergic T cells are distributed diffusely throughout the cell, whereas in primed T cells, pERK appears to be targeted to the same regions of the cell as the TCR. These data suggest that the different consequences of Ag recognition by T cells are associated with distinctive kinetics, amplitude, and localization of MAPK signaling.
|Number of pages||7|
|Journal||Journal of Immunology|
|Publication status||Published - 1 Aug 2004|
- ERK activation
- primary T cells
- laser scanning
Garside, P., Grierson, A. M., Harnett, M. M., Adams, C. L., & Mowat, A. M. (2004). Differences in the kinetics, amplitude, and localisation of ERK activation in anergy and priming revealed at the level of individual primary T cells by laser scanning cytometry. Journal of Immunology, 173(3), 1579-1586.