Decreased severity of myelin oligodendrocyte glycoprotein peptide 33 - 35-induced experimental autoimmune encephalomyelitis in mice with a disrupted TCR delta 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 gamma delta T cells in the regulation of EAE is unclear. We investigated gamma delta T cells in C57BL / 6 wild-type mice and C57BL / mice with a disrupted TCRdelta chain gene (delta(- / -) mice) using MOG p35 - 55. We found significantly less disease in delta(- / -) 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 delta(- / -) mice). Transfer of wild-type spleen cells restored the ability of delta(- / -) mice to develop equally severe EAE as wild-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-stimulated splenocytes from delta(- / -) mice. Enriched dendritic cells from delta(- / -) mice secreted significantly less TNF-alpha in response to lipopolysaccharide stimulation. Furthermore, when EAE was induced by adoptive transfer of an anti-MOG p35 - 55 alpha beta T cell line, there was a striking reduction 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 macrophages, 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 results demonstrate an impaired immune response in the delta(- / -) mouse that is associated with a defect in developing both actively induced and adoptively transferred EAE.

• Authors: T W Spahn, S Issazadah, A J Salvin, H L Weiner
• Journal: European journal of immunology (Eur J Immunol) Vol. 29 Issue 12 Pg. 4060-71 (12 1999) ISSN: 0014-2980 [Print] Germany
• PMID: 10602017 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antigens, Surface
• Mog protein, mouse
• Myelin Proteins
• Myelin-Associated Glycoprotein
• Myelin-Oligodendrocyte Glycoprotein
• Receptors, Antigen, T-Cell, gamma-delta

Topics

• Animals
• Antigens, Surface (immunology)
• Autoimmune Diseases (chemically induced, genetics, immunology)
• Encephalomyelitis (chemically induced, genetics, immunology)
• Gene Deletion
• Gene Expression Regulation (immunology)
• Mice
• Multiple Sclerosis (immunology)
• Myelin Proteins
• Myelin-Associated Glycoprotein (immunology, pharmacology)
• Myelin-Oligodendrocyte Glycoprotein
• Receptors, Antigen, T-Cell, gamma-delta (genetics, immunology)