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

Immunization of C57BL/6 mice with myelin oligodendrocyte glycoprotein (MOG) peptide (p) 35-55 induces chronic experimental autoimmune encephalomyeliti s (EAE). The role of gamma delta T cells in the regulation of EAE is unclea r. We investigated gamma delta T cells in C57BL/6 wild-type mice and C57BVm ice with a disrupted TCR delta chain gene (delta(-/-) mice) using MOG p35-5 5. We found significantly less disease in delta(-/-) mice immunized with MO G/complete Freund's adjuvant (mean maximal EAE score 4.3 +/- 0.8 in wild-ty pe vs. 2.3 +/- 0.5 in delta(-/-) mice). Transfer of wild-type spleen cells restored the ability of delta(-/-) mice to develop equally severe EAE as wi ld-type mice. In addition to IFN-gamma, IL-2, IL-5 and IL-10 was decreased in delta(-/-) mice. Decreased immune responses were also seen in delta(-/-) animals immunized with OVA peptide or protein and in concanavalin A-stimul ated splenocytes from delta(-/-) mice. Enriched dendritic cells from delta( -/-) mice secreted significantly less TNF-alpha in response to lipopolysacc haride stimulation. Furthermore, when EAE was induced by adoptive transfer of an anti-MOG p35-55 alpha beta T cell line, there was a striking reductio n of disease incidence (0%) and severity in delta(-/-) as compared to wild- type mice (83% incidence). delta(-/-) mice showed no cellular infiltration in the spinal cord whereas wild-type animals had infiltration of macrophage s, B cells, alpha beta- and gamma delta T cells. in adoptive transfer EAE, there was reduced IL-2 and IFN-gamma secretion in delta(-/-) mice. These re sults demonstrate an impaired immune response in the delta(-/-) mouse that is associated with a defect in developing both actively induced and adoptiv ely transferred EAE.