Differential expression of inhibitory receptors by regulatory T cells from mice with different susceptibility to autoimmune diseases

GLORIA JANET GODOY; SALAZAR, FLORENCIA C.; RUBEN DARIO MOTRICH; VIRGINIA RIVERO

Mar del Plata

Congreso; LXIV REUNIÓNANUAL DE SAI; 2016

Sociedad Argentina de Inmunologia

Differential Inhibitory Receptor expression in T regulatory cells from mice with different susceptibility to autoimmunity Gloria Janet Godoy1, Florencia Salazar1, Ruben Dario Motrich1, Virginia Elena Rivero1CIBICI-CONICET. Facultad de Ciencias Químicas. Universidad Nacional de Córdoba. ArgentinaNOD strain is characterized for its high susceptibility to develop spontaneous and induced autoimmune diabetes, thyroiditis, sialiditis and prostatitis. It has been suggested that this increased susceptibility could be related to defects in the number or functionality in regulatory T cells (Treg). Herein, we performed a comparative phenotype analysis between Treg from NOD, C57BL/6 and BALB /c mice. Therefore, we purified by cell sorting spleen CD4+CD25hi (Treg) and CD4+CD25-CD62Lhi (T naive) cells and performed Treg induction and Treg activation assays following standard procedures. Results obtained in Treg activation assays (CD4+CD25hicells + -CD3 and rIL-2 for 72 h) showed lower frequency and mean fluorescence intensity (MFI) for LAG-3, PDL-1 and PD-1 in Tregs from NOD mice compared to the other strains. TIM-3 showed high, medium and very mild density expression in Treg from C57BL/6, NOD and BALB/c mice, respectively. Results obtained in Treg induction assays (CD4+CD25-CD62Lhicells + TGF and rIL-2 for 5 days) showed less frequency and lower MIF for Foxp3, CD25, CTLA-4, LAG-3, LAP-1, CD39, PDL-1 and TIM-3 markers in NOD cultures when compared to values obtained in the other strains. These results manifest defects in both Treg induction and activation in the NOD strain and suggest that this lower capability to express inhibitory receptors could be related to its functionality and consequently to the high susceptibility to develop autoimmune diseases observed in this strain.