CIQUIBIC   05472
CENTRO DE INVESTIGACIONES EN QUIMICA BIOLOGICA DE CORDOBA
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Oral tratment with a hybrid protein betwenn E. coli heat labile toxin B subunit and ABC synapsin peptide reduced central nervous system inflammation in experimental autoinmune encephalomyelitis (EAE)
Autor/es:
BIBOLINI, MARIO J.; SCERBO, M. JULIA; PEINETTI, NAHUEL; ROTH, GERMAN A.; MONFERRÁN, CLARA G.
Lugar:
Buenos Aires
Reunión:
Congreso; First French-Argentine Immunology Congress; 2010
Resumen:
EAE is an established model for human multiple
sclerosis (MS). In both diseases autoreactive T cell clones are peripherally
generated and migrate into the central nervous system. Extensive inflammatory
reactions mediated by infiltrating mononuclear cells and production of
proinflammatory cytokines are responsible for demyelination, axonal disfunction
and neurological disability. We have previously shown that oral tolerance induced in rats with
LTBABC, a hybrid between the ABC domain of synapsin and the B
subunit of Escherichia coli
heat-labile enterotoxin (LTB) attenuated EAE clinical signs and diminished
cellular reactivity against myelin basic protein. To further characterize this
effect we analyzed histological changes and the presence of CD4+, CD8+,
CD45+CD11b+, CD4+ producing INF-γ or IL-17, and CD4+CD25+FoxP3+ cells
infiltrating CNS. Rats
were orally fed with 6 doses of LTBABC, LTB (0.3 nmol or equivalent amount in biological activity) or
vehicle after encephalitogenic challenge. Spinal cords and brains were obtained
during the EAE acute stage. Mononuclear cells infiltrating CNS were isolated
and analyzed by flow cytometry. Rats treated with LTBABC showed the fewest
inflammatory infiltrates in lumbar spinal cord sections stained with H & E
(p<0.01); and they also exhibited lower percentages of CD4+, CD8+ and CD4+cells
producing INF-γ than the ones fed with vehicle or LTB (p<0.05). Diminished
frequency of CD4+ IL-17+ cells were observed in the LTBABC group respect to
control group (p<0.05). Frequency of infiltrating macrophages (CD45+CD11b+
cells) did not differ between groups. CD4+CD25+FoxP3+ regulatory T cells were
expanded only in CNS of the LTBABC group (p<0.05). These results clearly
indicate that oral tolerance induced by LTBABC reduced infiltration of T cells
and increased the presence of CD4+CD25+FoxP3+ regulatory T cells in CNS,
suggesting that synapsin peptides coupled to LTB has a protective effect with
therapeutic potential in EAE and MS treatment.