CXCR3 and CCR5 chemokine receptors are crucial for diabetogenic T-cells to induce diabetes

BRESER, ML; KORF, H; MOTRICH, RD; VAN HOECK, J; GYSEMANS, C; MATHIEU, C; RIVERO, VE

Mar del Plata

Congreso; LIX Reunión Científica Anual de la SAIC ? LXII Reunión Científica Anual de la SAI; 2014

Sociedad Argentina de Investigación Clínica y Sociedad Argentina de Inmunologia

Type-1 diabetes is currently the most prevalent autoimmune disease worldwide. It is characterized by the destruction of beta cells by an autoimmune response that leads to insufficient or absent insulin production.NOD mice spontaneously develop a type-1 diabetes-like autoimmune disease, with the induction of specific Th1 and Tc1 immune responses. When activated, these Th1 or Tc1 cells express considerable levels of CXCR3 and CCR5 chemokine receptors suggesting the presence of organ-selective migration patterns. Herein, weaimed to advance in the current understanding of diabetogenic T cell migration patterns with special focus on CXCR3 and CCR5 chemokine receptors.Different experiments using NOD mice and TAK-779, a mimetic antagonist of CXCR3 and CCR5, were performed. Firstly and by control experiments, we ruled out the possibility that drug treatment affected macrophage and T cell activation or/and cytokine secretion abilities. On day 0, splenocytes from diabetic NOD mice were i.v. adoptively transferred into SCID-NOD recipient mice. From day 1 on, cell recipient mice were treated with TAK-779 (Treated) or vehicle (Control), and glycemia levels were monitored daily. After 4 weeks of continuous treatment, control animals showed a 100% diabetes incidence, while in treated animals it decreased up to 50% and remained stable for more than 10 weeks (p