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

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

Mar del Plata

Congreso; LXIV Reunión Anual de SAI, LXI Reunión Anual de la SAIC, XLVIII Reunión Anual de la SAFE, VII Reunión Anual de la NANOMEDAR, V Congreso Nacional de la AACyTAL.; 2016

Sociedad Argentina de Inmunologia

NOD mice are characterized for their high susceptibility to develop spontaneous and induced autoimmune diseases such as diabetes, thyroiditis, sialilitis and prostatitis. This increased susceptibility has been suggested to be related to defects in the number and/or the functionality of regulatory T cells (Tregs). Herein, we performed a comparative phenotypic analysis of Tregs from NOD, C57BL/6 and BALB /c mice. For that, using FACS, we purified spleen CD4+CD25hi (Tregs) and CD4+CD25-CD62Lhi (naïve) cells from the different mice strains under study and performed Tregs induction and activation assays following standard protocols. After performing Tregs activation assays, which consisted in the incubation of CD4+CD25hicells with -CD3 Abs and rIL-2 for 72 h, the expression of inhibitory receptors was analyzed. Lower cell frequencies expressing LAG-3, PDL-1 and PD-1, with also decreased mean fluorescence intensities (MFI) values, were found in Tregs from NOD mice when compared with C57BL/6 and BALB /c mice. Moreover, Tregs from C57BL/6, NOD and BALB/c mice showed high, medium and almost null TIM-3 expression, respectively. On the other hand, results from Tregs induction assays, which consisted in the incubation of CD4+CD25-CD62Lhi cells with rTGF and rIL-2 for 5 days, revealed lower cell frequencies expressing Foxp3, CD25, CTLA-4, LAG-3, LAP-1, CD39, PDL-1 and TIM-3, again with decreased MIF values, in Tregs from NOD mice when compared with C57BL/6 and BALB /c mice. These results indicate that Tregs from NOD mice have defects in both, their induction and activation abilities. These impairments to express inhibitory receptors could be related to defective functionality and, consequently, to the high susceptibility to develop autoimmune diseases observed in this strain.