GABA receptor composition and function on CD4+ T cells during the development of EAE.

FERNANDEZ HURST, N; ZANETTI, S.; BOUZAT C; ROTH G

Mar del Plata

Congreso; Reunión Anual Conjunta de la Sociedad Argentina de Investigación Clínica y Sociedad Argentina de Inmunología; 2014

Experimental autoimmune encephatomyelitis (EAE) is an animal model that mimicks many of the clinical and pathological features of the human diseases. Multiple sclerosis CD4+T cells aexert a critical role during the induction and development of the disease. In previous studies it was shown tha T cellsexpress GABAA receptors and in parallel in our laboratoryit was demonstrated that the treatment with Diazepam, an allosteric agonist of GABAA receptor, reduced the incidence and clinical signs of EAE. First of all, we evaluated the presence composition and fundamentally of GABAA recepors on CD4+T cells isolated from plopiteal lymph nodes of controls and EAE animals. Also the possible non-neuronal cell plasticity phenomenon was investigated in immune cells comparing with brain tissue. The animals were desentisized with myelin in complete Freund´s adjuvant (CFA) adjuvant to induce EAE or CFA alone as control group and sacrificed during the acute state of the disease (13-14 days post-induction). The mononuclear cells (MNC) were isolated from the draining plopiteal lympho nodes and the in vitro proliferation and the in vitro proliferation induced by anti-CD3 and in presence of GABAA agonists (GABA, Muscimol, Diazepam) was evaluated. GABAA agonists reduced the proliferation of CD4+T cells. The latter were also sorted and lysed in trizol to evaluate the subunit composition of GABAA receptor and a portion of frontal cortex tissue was obtained for comparison. We observed that CD4+T cells obtained from EAE animals do not have mRNA for Gamma2 subunit in contrast with CFA animals . We do not find the same difference in frontal cortext. These results indicate that GABAA agonists can modulate the proliferation of CD4+T cells, and we can also say that during the development of EAE occurs a non-neuronal cell plasticity phenomenon.