Phenotypic and functional differences in regulatory T cells from mice with different susceptibility to the development of autoimmune diseases

FLORENCIA SALAZAR; VIRGINIA E RIVERO; GLORIA J GODOY; RUBEN D MOTRICH

SANTIAGO

Workshop; FOCIS Goes South: Advances in Translational and Clinical Immunology Workshop; 2017

FCE Millennium Institute on Immunology and Immunotherapy

NOD mice are characterized by their highly susceptibility to develop spontaneous andinduced autoimmune diabetes, thyroiditis, sialiditis and prostatitis. It has been suggestedthat this increased susceptibility could be related to defects in the number and/orfunctionality in regulatory T cell (Treg) populations. In a previous work, we have shownthat NOD mice exhibited significantly lower frequencies and absolute Treg numbers whencompared to other mice strains. Herein, we analyze if NOD mice also exhibited phenotypicand functional differences within Treg populations. For that purpose, spleen CD4 + CD25 hi(Treg) cells from NOD, C57BL/6 and BALB/c mice were isolated by cell sorting and then invitro stimulated with anti-CD3, anti-CD28 and recombinant IL-2 for 72 h. After stimulation,Treg cells from NOD mice showed diminished inhibitory molecules expression. Indeed,Treg cells from NOD mice showed lower mean fluorescence intensity (MFI) values forCD39, LAG-3, PDL-1 and PD-1 when compared with C57BL/6 and BALB/c mice. Inaddition, a lower frequency and MFI values for Ki67 + were observed in NOD cultures.For functional studies, CD4 + CD25 - (T Conventional) cells were isolated by cell sorting andthen stimulated with anti-CD3/anti- CD28 in the presence different Treg ratios. Resultsshowed that Tregs from all strains suppressed T conventional proliferation. However,Tregs from NOD mice showed the lowest suppressive capacity when compared with theother strains (p