Visit our Expo - Redox and Inflammation signaling 2012

VIII. Inflammation specific signaling Poster VIII, 5
CD3 activation alters T cell responses to LFA-1 engagement: regulation of T cell
polarization and migration
Eva M. Cernuda-Morollón1, Federica Marelli-Berg2 and Anne J. Ridley1.
(1) Ludwig Institute for Cancer Research-UCL Branch, 91, Riding House Street, W1W
7BS London, UK. eva@ludwig.ucl.ac.uk; anne@ludwig.ucl.ac.uk (2) Department of
Immunology, Division of Medicine, Imperial College London, Du Canne Road, London
W12 ONN, UK. f.marelli@imperial.ac.uk.
Recognition of cognate antigen by the T cell receptor induces T cell proliferation. The
recruitment of these activated T cells to and retention at sites of inflammation are crucial for
the inflammatory response and therefore play an important role in pathological conditions
such as cardiovascular disorders and chronic inflammation. T cell recruitment requires them
to cross the endothelium, a process that involves multiple receptors including the integrin
LFA-1 on T cells, which binds to ICAM-1 on endothelial cells. We have observed that T cell
receptor activation, mimicked by cross-linking with anti-CD3 antibody, inhibits T cell
transendothelial migration. CD3 activation also reduces T cell migration speed on ICAM-1.
This effect is not due to changes in T cell adhesive properties and correlates with an
impairment in T cell polarization, as revealed by staining for different markers, including
CD44, ICAM-3 and lipid raft markers. Rho GTPases regulate actin and microtubule dynamics
and therefore cell polarization and migration. We are investigating the activation status of the
Rho GTPases RhoA, Rac1 and Cdc42. Pre-treatment with CD3 antibodies increases Rac1
activity and modulates T cell responses to LFA-1 engagement. Furthermore, CD3 activation
promotes stathmin/Op18 phosphorylation and increases the levels of acetylated alpha-tubulin,
both of which indicate an increase in microtubule stability.
We propose that CD3 activation affects actin and microtubule dynamics, thereby impairing
normal T cell polarization and migration.
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