Portal de Periódicos da CAPES

Decreased severity of myelin oligodendrocyte glycoprotein peptide 33 – 35-induced experimental autoimmune encephalomyelitis in mice with a disrupted TCR δ chain gene

1999; Wiley; Volume: 29; Issue: 12 Linguagem: Inglês

10.1002/(sici)1521-4141(199912)29

1521-4141

Thomas W. Spahn, Shoreh Issazadah, Anthony J. Salvin, Howard L. Weiner,

Immune Cell Function and Interaction

Immunization of C57BL / 6 mice with myelin oligodendrocyte glycoprotein (MOG) peptide (p) 35 – 55 induces chronic experimental autoimmune encephalomyelitis (EAE). The role of γ δ T cells in the regulation of EAE is unclear. We investigated γ δ T cells in C57BL / 6 wild-type mice and C57BL / mice with a disrupted TCRδ chain gene (δ– / – mice) using MOG p35 – 55. We found significantly less disease in δ– / – mice immunized with MOG / complete Freund's adjuvant (mean maximal EAE score 4.3 ± 0.8 in wild-type vs. 2.3 ± 0.5 in δ– / – mice). Transfer of wild-type spleen cells restored the ability of δ– / – mice to develop equally severe EAE as wild-type mice. In addition to IFN-γ, IL-2, IL-5 and IL-10 was decreased in δ– / – mice. Decreased immune responses were also seen in δ– / – animals immunized with OVA peptide or protein and in concanavalin A-stimulated splenocytes from δ– / – mice. Enriched dendritic cells from δ– / – mice secreted significantly less TNF-α in response to lipopolysaccharide stimulation. Furthermore, when EAE was induced by adoptive transfer of an anti-MOG p35 – 55 α β T cell line, there was a striking reduction of disease incidence (0 %) and severity in δ– / – as compared to wild-type mice (83 % incidence). δ– / – mice showed no cellular infiltration in the spinal cord whereas wild-type animals had infiltration of macrophages, B cells, α β- and γ δ T cells. In adoptive transfer EAE, there was reduced IL-2 and IFN-γ secretion in δ– / – mice. These results demonstrate an impaired immune response in the δ– / – mouse that is associated with a defect in developing both actively induced and adoptively transferred EAE.