How DCs Activate Resting Ts

Science's STKE  06 Feb 2001:
Vol. 2001, Issue 68, pp. tw2
DOI: 10.1126/stke.2001.68.tw2

Antigen-presenting cells (APCs), such as macrophages, and B cells can stimulate activated T cells. Dendritic cells (DCs) are specialized APCs that can potently activate resting (nonactivated) T cells. Within the regions of cell-to-cell contact between APCs and T cells, T cell antigen receptors aggregate to form a supramolecular signaling complex referred to as the immune synapse. Formation of the immune synapse requires the reorganization of the actin cytoskeleton in activated T cells, but actin reorganization in their cognate APCs does not appear to be required. It is unknown what is necessary for the activation of resting T cells. Al-Alwan et al. observed the intracellular rearrangements that occur during the contact of DCs and resting T cells and found that clustering of T cells at the surface of DCs correlated with cytoskeletal reorganization in DCs in vitro, as measured by fascin (an actin-bundling protein) and actin polymerization. Pretreatment of either resting T cells or DCs with cytochalasin D (CytD) or jasplakinolide, toxins that prevent actin reorganization, greatly reduced cell-to-cell clustering between DCs and resting T cells, and also prevented the activation of resting T cells. However, clustering of activated T cells with DCs was not diminished when DCs were pretreated with CytD, a finding that parallels the unimportance of cytoskeletal rearrangement in B cell stimulation of activated T cells. Thus, actin reorganization is required in DCs before the activation of resting T cells. Cytoskeletal reorganization might act to increase the contact surface area between the cells, leading to stronger signals generated in the synapse to activate resting T cells and thus explaining why DCs are such potent activators of resting T cells.

M. M. Al-Alwan, G. Rowden, T. D. G. Lee, K. A. West, Cutting edge: The dendritic cell cytoskeleton is critical for the formation of the immunological synapse. J. Immunol. 166: 1452-1456 (2001). [Online Journal]