Apoptosis

TRAIL-expressing T cells induce apoptosis of vascular smooth muscle cells in the atherosclerotic plaque. Sato, K. et al. J. Exp. Med. 17 Jan 2006 (doi:10.1084/jem.20051062)

Rupture of atherosclerotic plaques is a frequent cause of acute coronary syndromes (ACSs), such as myocardial infarction. In this paper, plaque-infiltrating activated CD4+ T cells were shown to contribute to plaque instability. In vitro, plaque-derived CD4+ T cells could effectively kill vascular smooth-muscle cells (VSMCs). Killing was mediated through death receptor 5 (DR5) expressed by VSMCs, as incubation with antibodies specific for the DR5 ligand TRAIL inhibited T-cell killing of VSMCs. In vivo, adoptive transfer of plaque-derived CD4+ T cells to immunodeficient mice bearing human plaque implants resulted in apoptosis of VSMCs, which was prevented by co-administration of TRAIL-specific antibody. Importantly, patients with ACS have a higher frequency of TRAIL-expressing CD4+ T cells in the blood compared with controls, indicating that these cells might be involved in plaque rupture.

T-cell signalling

Direct manipulation of activator protein-1 controls thymocyte proliferation in vitro. Thornton, T. M. et al. Eur. J. Immunol. 36, 160–169 (2006)

While studying the role of BATF (activating transcription factor B) in thymocyte proliferation, Thornton et al. unexpectedly observed that certain conditions of T-cell stimulation inhibit the transcription of transgenes under the control of the Lck promoter, a system that is widely used in T-cell studies. Consistent with the function of BATF as an inhibitor of activator protein 1 (AP1)-driven transcription, stimulation of Batf-transgenic T cells with CD3-specific and CD28-specific antibody or concanavalin A inhibited proliferation. However, when these T cells were stimulated with PMA and ionomycin, proliferation was normal. This was the result of unexpected downregulation of Lck-promoter-driven transcription and rapid loss of BATF protein. Nevertheless, the authors went on to show that inhibition of AP1 activity by BATF has a direct and reversible effect on T-cell proliferation in vitro.

Autoimmunity

Human plasmacytoid pre-dendritic cells activate NK cells through glucocorticoid-induced tumor necrosis factor receptor-ligand (GITRL). Hanabuchi, S. et al. Blood 5 Jan 2006 (doi:10.1182/blood-2005-08-3419)

To investigate, at the molecular level, how plasmacytoid dendritic cells (pDCs) regulate immune responses, Hanabuchi et al. carried out microarray analyses of unactivated human pDCs and pDCs activated by herpes simplex virus 1 or influenza virus A. Expression of mRNA encoding glucocorticoid-induced TNF-receptor-related protein ligand (GITRL) by pDCs was upregulated following activation by viruses. Consistent with this, GITRL expression was increased on the cell surface of pDCs following activation by viruses or CpG DNA. Natural killer (NK) cells express high levels of the receptor for GITRL and pDCs activated by CpG DNA induced NK-cell cytotoxicity and interferon-γ (IFNγ) production in a GITRL-dependent manner. Such GITRL-mediated co-stimulation of NK cells required the presence of IFNα and provides a new mechanism of NK-cell–pDC crosstalk.