Induction of T Cells With Regulatory Capacity By Embryonic Neural Cells
Posted on: Thursday, 17 June 2004, 06:00 CDT
Aim. We have analyzed the capacity of an immortalized neural cell line, obtained from mouse midbrains at day 11 of gestation (A1 cells), to alter T cell proliferation and differentiation. Methods. Co-culture of mouse CD4^sup +^ T cells with Al cells induced a contact-dependent regulatory T cell phenotype characterized by reduced proliferation, low levels of interferon-g (IFN-[gamma]) and increased secretion of transforming growth factor-b (TGF-[beta]). These A1-induced regulatory T cells were hyporesponsive upon a secondary stimulation with anti-CD3 antibody. This condition was reversible with exogenous interleukin-2 (IL-2) replacement. Results. At biochemical level, CD4^sup +^ T cells, co-cultured with A1 cells and activated with anti-CD3/CD28, showed reduced tyrosine- phosphorilation of the extracellular-signal regulated kinase 1/2 (ERK1/2) and the failure to downregulate the cyclin-depcndent kinase inhibitor p27 (p27^sup kip-1^). Finally, T cells activated in the presence of Al cells were able in vivo, upon passive transfer, to suppress induction and progression of an animal model of multiple sclerosis (experimental autoimmune encephalomyelitis, RAE). Conclusion. Our results provide a rationale for the usage of embryonic neural cells in the generation of T cells with regulatory/ suppressor properties.
G. Matarese1, V. Sanna1, U. Di Porzio2, L. Colucci1,2
1Group of Immunoendocrinology, Unit of Endocrinology and Experimental Oncology, IESO-CNR, Naples, Italy, laboratory for Molecular, Cell and Development Neurobiology, A. Buzzati-Traverso Institute for Genetics and Biophysics, IGB-CMR, Naples, Italy
Copyright Edizioni Minerva Medica Mar 2004
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