Triiodothyronine (T3) promotes the development of an antigen-specific cytotoxic response through modulation of dendritic cell (DC) function
Alamino VA1; Mascanfroni ID1; Montesinos MM1; Susperreguy S1; Masini-Repiso AM1; Rabinovich GA2; Pellizas CG1.
1Centro de Investigaciones de Bioqu¨ªmica Cl¨ªnica e Inmunolog¨ªa (CIBICI-.CONICET). Facultad de Ciencias Qu¨ªmicas. Universidad Nacional de C¨®rdoba, Argentina.
2Instituto de Biolog¨ªa y Medicina Experimental (IBYME-CONICET) Argentina
Mice DC, the main antigen presenting cells, express thyroid hormone receptor beta 1 (TRb1) and physiological levels of triiodothyronine (T3) stimulates DC maturation and strengthens their T cell allostimulatory capacity directing a T1-type cytokine response (Mascanfroni et al. 22:1032,2008). In this study we investigated the ability of T3-stimulated DC to modulate 1) antigen-specific cytotoxicity in vivo and 2) antigen cross-presentation in vitro. For 1) and according to Calvo et al (J Immunol 181: 408,2008), DC were pulsed with OVA+T3 (5nM) for 30 min and i.v. injected to C57BL/6 mice. After 7 days mice were i.v. injected with a splenocyte mix (1:1;control:OVA257-264) stained with CFSE in two concentrations (0.5mM control:3¦ÌM OVA257-264). After 24 h, CFSE stained cell abundance from spleens was determined by flow cytometry. For 2) and in agreement to Fu et al (J Immunol Methods 335:90,2008) an overnight co-culture of DC pulsed with OVA+T3 and B3Z hybridoma cells (recognize OVA when presented via MHC I) was carried out. Levels of b-Gal (which expression is controlled by IL-2 promoter) were measured in supernatants. Our results indicated that 1) T3 significantly increased DC ability to stimulate a cytotoxic antigen-specific response, revealed by reduction of 3mM CFSE stained cells, 2) T3 significantly increased OVA cross-presentation evaluated through the increase of bGal expression. Our findings provide evidence for a critical role of T3 in the induction of a cytotoxic response that may have profound implications in immunotherapy including cancer, and broaden the knowledge of the interplay between immune and endocrine systems.