PERONE Marcelo Javier
Transgenic Galectin-1 Induces Maturation of Dendritic CellsThat Elicit Contrasting Responses in Naive and Activated T Cells1
PERONE, M.J.; LARREGINA, A. T.; SHUFESKY, W. J.; PAPWORTH, G. D.; SULLIVAN, M.L.G.; ZAHORCHAK, A. F.; BEER STOLZ, D; BAUM, L. G.; WATKINS, S. C.; THOMSON, A. W.; MORELLI, A. E.
JOURNAL OF IMMUNOLOGY
AMER ASSOC IMMUNOLOGISTS
Lugar: Amer Assoc Immunologist; Año: 2006 p. 7207 - 7207
Abstract Dendritic cells (DC) are professional APC that control the balance between T cell immunity and tolerance. Genetic engineering of DC to regulate the outcome of the immune response is an area of intense research. Galectin (gal)-1 is an endogenous lectin that binds to glycoproteins and exerts potent regulatory effects on T cells. Consequently, gal-1 participates in central deletion of thymocytes and exerts therapeutic effects on experimental models of T cell-mediated autoimmune disorders and graft-vs-host disease. Together, these observations strongly indicate that engineering DC to express transgenic (tg) gal-1 may be beneficial to treat T cell-mediated disorders. In this study, we have investigated the impact of the expression of high levels of tg gal-1 on maturation/activation of DC and on their T cell stimulatory function. Murine DC were transduced with a recombinant adenovirus encoding hu gal-1 (gal-1-DC). Tg gal-1 was exported by a nonclassical pathway through exosomes and was retained on the DC surface inducing segregation of its ligand CD43. Expression of tg gal-1 triggered activation of DC determined by induction of a more mature phenotype, increased levels of mRNA for proinflammatory cytokines, and enhanced ability to stimulate naive T cells. Conversely, gal-1-DC induced rapid apoptosis of activated T cells. In vivo, gal-1-DC increased significantly the sensitization phase of contact hypersensitivity assays while inducing a drastic inhibition of the elicitation phase by triggering apoptosis of activated T cells in the dermis. Gal-1-DC represent a novel tool to control differentially the afferent and efferent arms of the T cell response. The Journal of Immunology, 2006, 176: 72077220.The Journal of Immunology, 2006, 176: 72077220.