In:
The Journal of Immunology, The American Association of Immunologists, Vol. 165, No. 12 ( 2000-12-15), p. 7157-7163
Abstract:
High-dose Ag administration induces apoptotic death of autoreactive T cells and is an effective therapy of experimental autoimmune diseases of the nervous system. To explore the role of cytokines in Ag-specific immunotherapy, we analyzed mRNA induction and protein expression for the proinflammatory cytokines TNF-α and IFN-γ, the anti-inflammatory cytokine IL-10, and the cytokine-inducible NO synthase (iNOS) during high-dose Ag therapy of adoptive transfer experimental autoimmune encephalomyelitis (AT-EAE) in the Lewis rat. Using semiquantitative and competitive RT-PCR, we found 5- to 6-fold induction of TNF-α mRNA and 3-fold induction of IFN-γ mRNA in the spinal cord that occurred within 1 h after i.v. injection of Ag and was accompanied by a 2-fold increase of iNOS mRNA. Both IFN-γ and iNOS mRNA remained elevated for at least 6 h, whereas TNF-α mRNA was already down-regulated 6 h after Ag injection. A comparable time course was found for circulating serum levels of TNF-α and IFN-γ. IL-10 mRNA levels did not change significantly following Ag injection. Neutralization of TNF-α by anti-TNF-α antiserum in vivo led to a significant decrease in the rate of T cell and oligodendrocyte apoptosis induced by high-dose Ag administration, but did not change the beneficial clinical effect of Ag therapy. Our data suggest profound activation of proinflammatory but not of anti-inflammatory cytokine gene expression by high-dose Ag injection. Functionally, TNF-α contributes to increased apoptosis of both autoaggressive T cells and oligodendrocytes in the target organ and may thereby play a dual role in this model of Ag-specific therapy of CNS autoimmune diseases.
Type of Medium:
Online Resource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.165.12.7157
Language:
English
Publisher:
The American Association of Immunologists
Publication Date:
2000
detail.hit.zdb_id:
1475085-5
