Book of Abstracts - Australian Centre for Economic Research on ...

23-26 August 2007,
Budapest, Hungary
ceramide cSrc – phosphoprotein steps mediate the early IL-1 response. After 45-60 min the classical Toll
signaling pathway involving the NFKB mediated induction <strong>of</strong> COX2 and the subsequent production <strong>of</strong> the
inflammatory mediator PGE2.
The chronic inflammatory stress presented by obesity and the role <strong>of</strong> IL-1 in the conversion from insulin
resistance to type 2 diabetes will also be discussed.
258
5D_03_S
ROLE OF LIPIDS IN THE MODULATION OF HUMAN T CELL ACTIVATION
T. Fulop 1 , P. Brassard 2 , A. Larbi 1 , F. Frisch 2 , C. Fortin 1 , A. Carpentier 2
1Division <strong>of</strong> Geriatrics and the Program <strong>of</strong> Immunology, 2 Division <strong>of</strong> Endocrinology, Department <strong>of</strong> Medicine,
University <strong>of</strong> Sherbrooke, Sherbrooke, Qc, Canada
Studies have shown suppressive effects <strong>of</strong> PUFA on T cell functions suggesting that lipids can have potent
immunomodulatory effects. It is now accepted that the membrane <strong>of</strong> T cells is heterogeneous and contains
microdomains called lipid rafts (LR) playing an important role in TCR signalling. Thus, variations in lipid
levels and composition may determine their effects on immune response. Each time when lipids are ingested
the immune system is submitted to a lipid stress. The precise mechanism <strong>for</strong> this effect has not been fully
investigated in vivo in humans. Our aim was to determine whether there are differences in T cell functions and
signalling depending on the way <strong>of</strong> lipid administration and composition. Peripheral T cells were isolated
from healthy subjects be<strong>for</strong>e and after 2-hours <strong>of</strong> an intravenous infusion <strong>of</strong> heparin + Intralipid (HI) during
a euglycemic hyperinsulinemic clamp to induce a 2.5-fold elevation in plasma linoleic acid concentration.
Similar experimental setting was designed after an oral meal (OM).. HI and OM reduced peripheral T cell
membrane fluidity and altered lipid raft organisation. Both associated with reduced T cell proliferation upon
CD3 + CD28 co-stimulation. Tyrosine phosphorylation <strong>of</strong> LAT and activation <strong>of</strong> Akt in T cells were also
impaired without a reduction in T cell receptor expression. The LR polarization was also altered. A selective
increase in plasma linoleic acid concentration and in intravascular lipolysis there<strong>for</strong>e have a suppressive effect
on peripheral T cell CD28-dependent activation and this effect associates with changes in plasma membrane
properties. The lipid composition <strong>of</strong> nutritional therapy in patients at high risk <strong>of</strong> septic complications may be
crucial and may also be <strong>of</strong> relevance <strong>for</strong> type 2 diabetes. Furthermore, oral nutrition rich in lipids constituting
a chronic lipid stress, at long term, could contribute to the observed immunosenescence.
5D_04_S
NEUROENDOCRINE RESPONSE IN SUSCEPTIBILITY TO INFLAMMATORY,
AUTOIMMUNE AND INFECTIOUS DISEASES
Esther M. Sternberg
NIMH/NIH, Bethesda, MD, USA
The central nervous system (CNS) plays an important role in regulating immunity and in susceptibility and
resistance to autoimmune, inflammatory and infectious diseases. Cytokines released during inflammation
mediate changes in brain function, inducing sickness behaviors, sleep, fever and activation <strong>of</strong> the hormonal
stress response (hypothalamic-pituitary-adrenal axis, HPA axis). In turn neural and neuroendocrine responses,
including the HPA axis, sympathetic and parasympathetic responses, regulate immune responses, thus
providing important extra-immune system feedback control <strong>of</strong> immunity. HPA axis activation inhibits
inflammation through the generally anti-inflammatory action <strong>of</strong> the glucocorticoids. However, physiologic