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

Abstract

Immunization of C57BL/6 mice with myelin oligodendrocyte glycoprotein (MOG) peptide (p) 35-55 induces chronic experimental autoimmune encephalomyelitis (EAE). The role of γδ T cells in the regulation of EAE is unclear. We investigated γδ 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 αβ 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, αβ- and γδ 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.