Functional differences in regulatory t cells from mice with different susceptibility to the development of autoimmune diseases

GODOY, GLORIA J.; SALAZAR, FLORENCIA C.; OLIVERA, CAROLINA; MOTRICH, RUBEN D.; RIVERO, VIRGINIA E.

Buenos Aires

Congreso; Reunion Conjunta de sociedades en Biociencias; 2017

Sociedad Argentina de Inmunologia,Sociedad Argentina de Investigación Clinica, Sociedad Argentina de Farmacología Experimental,Sociedad Argentina de Biologia, Sociedad Argentina de Andrología , entre otras

NOD mice are characterized by their highly 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 and/or functionality in regulatory T cell (Treg) populations. In a previous work, we have shown that NOD mice exhibited significantly lower frequencies, absolute Treg numbers and mean fluorescence intensity (MFI) for Foxp3, when compared with other mice strains (p<0.05). Herein, we analyze if NOD mice also exhibited functional differences within Treg populations. For that purpose, spleen CD4+CD25hi (Treg) cells from NOD, C57BL/6 and BALB/c mice were isolated by cell sorting and then in vitro activated with anti-CD3, anti-CD28 and different doses of recombinant IL-2 (0,50 and 200 U/I). After stimulation in the presence of rIL-2, Treg cells from NOD mice showed lower frequencies of Foxp3+ CD25+ when compared with C57BL/6 and BALB/c mice+ (p<0.05). Moreover, Treg cells from NOD mice showed diminished expression for Foxp3 and CD25 even with the addition of high rIL2 doses. Furthermore, a lower frequency and MFI values for Ki67 were observed in Treg NOD cultures even after rIL2 stimulation. To evaluate Treg suppression capabilities, CD4+CD25- (T Conventional) cells were isolated by cell sorting and then stimulated with anti-CD3/anti-CD28 at different Tconv/Treg ratios. Results showed that Tregs from all strains suppressed T conventional proliferation. However, Tregs from NOD mice showed the lowest suppressive capacity when compared with the other strains (p<0.05). Our results show that Tregs from NOD mice have defects in their activation and suppression abilities. The defective functionality found could be related to the high susceptibility to develop autoimmune diseases observed in NOD mice