Characterization and functional analysis of regulatory T cells (Tregs) from mice with differential susceptibility to autoimmunity

GODOY, GLORIA J.; SANCHEZ, LEONARDO R.; MOTRICH, RUBEN D.; RIVERO, VIRGINIA E.

Buenos Aires

Congreso; LXIII Reunión Anual de SAI, I Meeting LASID-SAI-FAIC, IV Meeting LASID, y II Meeting FAIC.; 2015

Sociedad Argentina de Inmunologia

BackgroundWhile NOD mice are highly susceptible to develop spontaneous and induced autoimmunity, other strains are moderately prone (C57BL/6) or resistant (BALB/c). That high susceptibility has been related to defects in Tregs populations. Herein, we analyzed and compared the phenotype and functionality of Tregs from those different mice strains.MethodsSpleen and lymph node mononuclear cells (MNC) from NOD, C57BL/6 and BALB/c were obtained in steady state conditions (up to 8 weeks old). Tregs were stained (CD4+FoxP3+) and analyzed by FACS. CD4+CD25+ and CD4+CD25- MNC were sorted and activation and suppression assays were performed.ResultsSignificantly increased frequencies of CD4+CD25+Foxp3+, CD4+Foxp3+Helios+Nrp1+, and CD4+Foxp3+CCR6+ Tregs populations were observed in BALB/c mice (p <0.05). However, no differences in the MFI values of Foxp3, CXCR3, GITR, CTLA-4, and CD25 were observed in Tregs among the different animal strains. Nevertheless, when Tregs were sorted and activated in vitro with anti-CD3, anti-CD28 and IL-2, increased MFI values of CD25 and GITR were observed in Tregs from BALB/c mice. Although, no differences in FOXP3, CTLA-4 and IL-10 were detected among all animal strains. Finally, sorted Tregs from all animal strains suppressed anti-CD3/anti-CD28-induced CD4+CD25- MNC proliferation. Notwithstanding, Tregs from BALB/c mice showed the highest suppressive capacity (p <0.05). Conclusions Our results show that, in steady state conditions, BALB/c mice have increased numbers and functional Tregs compared to other mice strains (NOD and C57BL/6). That could be related to the natural resistance of BALB/C mice to the induction or development of autoimmunity.