CD28-B7 costimulation: a critical role for initiation and development of experimental autoimmune neuritis in C57BL/6 mice.
CD28 provides a critical costimulatory signal for antigen-specific T cell activation. Because CD28 is an important factor in the development of autoimmune diseases, we investigated its role in T cell-mediated experimental autoimmune neuritis (EAN), an animal model of Guillain-Barré syndrome in humans. CD28-deficient mutant (CD28-/-) C57BL/6 mice and corresponding wild-type mice were immunized with P0 peptide 180-199, a purified component of peripheral nerve myelin, and Freund's complete adjuvant. As a result, all wild-type mice developed severe EAN, in contrast, none of the CD28-/- mice manifested clinical signs of disease. Additionally, CD28-/- mice had fewer IL-12 producing cells in sciatic nerve sections and fewer IFN-gamma secreting splenic cells than wild-type mice on day 24 post immunization, i.e., at the peak of clinical EAN. At that time point, CD28-/- mice had milder infiltration of such inflammatory cells as macrophages, CD4+ T cells and monocytes into sciatic nerve tissues and less demyelination than wild-type mice. Moreover, the CD28-deficiency led to reduced production of specific anti-P0 peptide 180-199 antibodies compared with wild-type mice. Evidently, CD28 is required for interaction with B7 to regulate the activation of T and B cells that initiates development of EAN.
Division of Geriatric Medicine (B84), Department of Clinical Neuroscience, Karolinska Institutet, Huddinge University Hospital, S-141 86 Huddinge, Stockholm, Sweden. jie.zhu@neurotec.ki.se
Y
Y
Zhu
H
H
Ljunggren
E
E
Mix
H L
HL
Li
P
P
van der Meide
A M
AM
Elhassan
B
B
Winblad
J
J
Zhu
D000818:Animals; D018122:B7-1 Antigen / Q000276:immunology*; D018106:CD28 Antigens / Q000235:genetics* / Q000276:immunology*; D004195:Disease Models, Animal; D020275:Guillain-Barre Syndrome / Q000235:genetics / Q000276:immunology / Q000473:pathology; D007074:Immunoglobulin G / Q000097:blood; D018664:Interleukin-12 / Q000096:biosynthesis; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018993:Myelin P0 Protein / Q000276:immunology; D009444:Neuritis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D010446:Peptide Fragments / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
D018122:B7-1 Antigen; D018106:CD28 Antigens; D007074:Immunoglobulin G; D018993:Myelin P0 Protein; D010446:Peptide Fragments; D018664:Interleukin-12