INVESTIGADORES
PERONE Marcelo Javier
congresos y reuniones científicas
Título:
Disease-modifying immunotherapy for the management of autoimmune diabetes
Autor/es:
PERONE, M.J.
Lugar:
Buenos Aires
Reunión:
Simposio; III Iberoamerican Congress on NeuroImmunoModulation; 2009
Resumen:
Type 1 diabetes (T1D) is a T cell-mediated autoimmune disease that destroys the insulin-secreting β-cells of the pancreas. At present, it is possible to predict with accuracy those candidates that will progress to T1D much before the full onset of the disease. Therefore, a prophylactic approach directed to inhibiting the function of self-reactive T cell clones as soon as they become activated would be beneficial for prevention of T1D or potential recurrence of the specific anti-β-cell autoimmunity in transplanted islets.Dendritic cells (DC) are the most potent antigen-presenting cells (APC) for the activation of naive and memory T cells and, together with B cells, are intimately involved in the initiation of the T cell response that triggers β-cell destruction. However, DC also participate in induction/maintenance of central and peripheral T cell tolerance and a failure of DC to present tolerogenic peptides to thymocytes during central deletion may be the cause of T1D. It is feasible enhance DC ability to down-regulate the T cell response by means of pharmacological and gene therapy methods with the objective of generating regulatory-DC for treatment of T cell-mediated autoimmune disorders. Although, most current DC-based approaches to treat autoimmune disorders are focused at interfering with the ability of DC to activate naive T cells, once T cells become activated, most conventional DC-based therapies are unable to inhibit the function of effector T cells. As occurs in T1D and other autoimmune disorders, the signs/symptoms that lead to diagnosis are detected after the onset of disease, when self-reactive T cells are fully activated. Therefore, strategies that target the deletion of activated self-reactive T cells early in the progression of the disease are warranted, because they would allow for the preservation of residual β-cell mass.Galectin (gal)-1 is an endogenous lectin that participates in T cell homeostasis maintenance. Gal-1 induces rapid death of activated T cells through a mechanism that is Fas-Fas ligand independent and it plays an important role in peripheral T cell suppression and/or tolerance. The potent regulatory effects of gal-1 on activated T cells, including induction of apoptosis and down-modulation of the Th1 response, makes this endogenous lectin a potentially useful therapeutic protein for T1D treatment.I shall present data recently obtained by both, cell-based gene and pharmacology therapies employing gal-1 and discuss its beneficial effects on prevention and cure of T1D in the workhorse model of disease, the NOD mice. The use of the potent immunoregulatory properties of gal-1 is a novel approach to control the T cell autoimmune response that triggers T1D.