CD4 and CD8 T cells, but not B cells, are critical to the control of murine experimental autoimmune neuritis.
Experimental autoimmune neuritis (EAN) is a T cell-mediated autoimmune disease of the peripheral nervous system that duplicates the clinical, pathological, and electrophysiological features of Guillain-Barré syndrome in humans. However, the molecular pathogenesis of EAN remains controversial. Therefore, for this study, we induced EAN with P0 protein peptide 180-199 in CD4(-/-), CD8(-/-), CD4(-)8(-), and B cell knockout (microMT) mice to further investigate the roles of these cells in EAN. Our results showed that the severity of clinical signs and histopathological manifestations of EAN and the T cell response to P0 peptide 180-199 in CD4(-/-) mice were significantly lower than those in their wild-type counterparts. CD8(-/-) mice also had a milder clinical course, less histopathological change, and a diminished T cell response to P0 peptide 180-199. However, more severe clinical and histopathological manifestations, a stronger T cell response to P0 peptide 180-199, and enhanced IFN-gamma production in the spleen were observed in the EAN of CD4(-)8(-) and microMT mice, but these were not obviously different from those of wild-type mice. Levels of IgG production were similar in sera from CD4(-/-), CD8(-/-), and CD4(-)8(-), and wild-type mice. These findings suggest that the induction and control of murine EAN are dependent on both CD4(+) and CD8(+) T cells and that B cells apparently do not perpetuate the related inflammatory demyelination.
Zhu
Yu
Y
Division of Geriatric Medicine, Department of Neurotec, Department of Medicine, Karolinska Institutet, Huddinge University Hospital, S-14186, Stockholm, Sweden.
Bao
Lei
L
Zhu
Shunwei
S
Chen
Zhiguo
Z
van der Meide
Peter
P
Nennesmo
Inger
I
Winblad
Bengt
B
Ljunggren
Hans-Gustaf
HG
Zhu
Jie
J
D000818:Animals; D000918:Antibody Specificity; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D020278:Demyelinating Autoimmune Diseases, CNS / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood; D007249:Inflammation / Q000276:immunology; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009444:Neuritis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
D007074:Immunoglobulin G