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. 1997 Jun 16;185(12):2177-82.
doi: 10.1084/jem.185.12.2177.

Tumor necrosis factor alpha and lymphotoxin alpha are not required for induction of acute experimental autoimmune encephalomyelitis

K Frei  1 , H P Eugster, M Bopst, C S Constantinescu, E Lavi, A Fontana
Affiliations

Tumor necrosis factor alpha and lymphotoxin alpha are not required for induction of acute experimental autoimmune encephalomyelitis

K Frei et al. J Exp Med. .

Abstract

Immunization of mice with myelin components results in experimental autoimmune encephalomyelitis (EAE), which is mediated by myelin-specific CD4(+) T cells and anti-myelin antibodies. Tumor necrosis factor alpha (TNF-alpha) and lymphotoxin alpha (LT-alpha) are thought to be involved in the events leading to inflammatory demyelination in the central nervous system. To ascertain this hypothesis 129 x C57BL/6 mice with an inactivation of the tnf and lta genes (129 x C57BL/6(-/-)) and SJL/J mice derived from backcrosses of the above mentioned mutant mice (SJL-/-) were immunized with mouse spinal cord homogenate (MSCH) or proteolipid protein. Both 129 x C57BL/6(-/-) mice and SJL-/- mice developed EAE. In SJL-/- mice immunized with MSCH, a very severe form of EAE with weight loss, paralysis of all four limbs, and lethal outcome was observed. The histologic hallmark was an intense perivascular and parenchymal infiltration with predominantly CD4(+) T cells and some CD8(+) T cells associated with demyelination in both brain and spinal cord. These results indicate that TNF-alpha and LT-alpha are not essential for the development of EAE.

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Figures

Figure 1
Figure 1
Histopathologic analysis of spinal cord and brains from TNF- and LT-α–deficient mice with acute EAE after immunization with MSCH. (A) Perivascular infiltrates in spinal cord (longitudinal section, hematoxilin and eosin stain) and (B) demyelination in areas of cell infiltrates in brain tissue (Luxol fast blue stain). Mononuclear cells in brain tissue consists mainly of CD4+ T lymphocytes (C) and CD8+ T cells (D) as shown by immunohistochemistry. Staining was performed on 1-μm paraffin sections (A and B) or 3-μm cryosections (C and D). Original magnifications of A and B, 200; C and D, 500.
Figure 2
Figure 2
RT-PCR cytokine transcripts from wild type and TNF- and LT-α–deficient mice during acute EAE. Transcripts from different tissues (br, brain; sc, spinal cord; sp, spleen) from acute EAE induced with PLP or MSCH from representative mice are shown.
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