EFFECTS OF DIAZEPAM ON CD4 T CELLS IN EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS (EAE)

FERNÁNDEZ HURST, NICOLÁS; ZANETTI SAMANTA R.; BOUZAT CECILIA B.; ROTH, GERMAN A.

Buenos Aires

Congreso; I Meeting LASID, FAIC and SAI; 2015

Sociedad Argentina de Inmunología (SAI)

CD4 T cells exert a critical role during the induction and development of EAE. Diazepam (Dz) is an allosteric agonist of the GABA-A receptor (GABA-AR) and also binds to the peripheral benzodiazepine receptor, TSPO. Previously, we demonstrated that Dz has a protective role during the development of EAE. In this study, we investigated how Dz mediates this action. The animals were sensitized with complete Freund?s adjuvant (CFA) alone as control group or with myelin to induce EAE, treated with various Dz concentrations, and sacrificed during the acute state of the disease. We evaluated the proliferation of isolated CD4 draining popliteal lymph node T cells in presence of Concanavalin A, Dz and Pk11195 (a specific antagonist of TPSO). Dz reduces the proliferation of CD4 T cells, Pk11195 partially blocks the effect of Dz only in CFA group (p<0.05). Then, we evaluated the expression of the γ2 subunit of GABA-AR and TPSO by qPCR in CD4 T cells and in nervous cortex tissue for comparison. We observed that the levels of γ2 subunit and TPSO were reduced in CD4 T cells from EAE animals treated or not with Dz in comparison to CFA animals (p<0.05). However, in cortex the levels of γ2 subunit did not change but TSPO levels increased in EAE animals. These results indicate a differential effect of Dz in the proliferation of CD4 T cells between CFA and EAE animals and there is not a correlation between the expression of receptors in peripheral immune cells and neural tissue.