Treatment and prevention of experimental autoimmune neuritis with superagonistic CD28-specific monoclonal antibodies.
Two distinct CD28-specific mAb were used in treatment of active or adoptive transfer (AT)-experimental autoimmune neuritis (EAN): "superagonistic" JJ316 activates T cells without T cell receptor (TCR) occupancy, and conventional JJ319 activates T cells only in the presence of TCR-stimulation. Treatment with JJ316 during induction phase of active and adoptive-transfer experimental autoimmune encephalomyelitis (AT-EAN) dramatically reduced disease severity and improved nerve function as revealed by electrophysiology. JJ316 given 1 week before immunization had a preventive effect. By immunohistology, JJ316 markedly reduced TC infiltration of the sciatic nerve in active and AT-EAN. JJ319 was less effective. Ex vivo, JJ316 therapy reduced P2-specific proliferation and interferon-gamma (IFN-gamma) production of lymph node cells. We demonstrate preventive and therapeutic effects of a "superagonistic" mAb-mediated, TCR-independent CD28 stimulation in EAN, possibly with implications for therapy of autoimmune-inflammatory disorders.
Schmidt
Jens
J
Department of Neurology, University of Würzburg, Josef-Schneider-Str. 11, D-97080, Würzburg, Germany.
Elflein
Karin
K
Stienekemeier
Martina
M
Rodriguez-Palmero
Marta
M
Schneider
Christiane
C
Toyka
Klaus V
KV
Gold
Ralf
R
Hünig
Thomas
T
D019264:Adoptive Transfer; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000627:therapeutic use*; D018106:CD28 Antigens / Q000276:immunology*; D002455:Cell Division / Q000276:immunology; D002460:Cell Line; D002465:Cell Movement / Q000276:immunology; D002478:Cells, Cultured; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D007110:Immunity, Active; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use; D007274:Injections, Intraperitoneal; D007371:Interferon-gamma / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000276:immunology; D018996:Myelin P2 Protein / Q000276:immunology; D009444:Neuritis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D010446:Peptide Fragments / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D012584:Sciatic Nerve / Q000276:immunology / Q000503:physiopathology; D012720:Severity of Illness Index; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000637:transplantation
D000911:Antibodies, Monoclonal; D018106:CD28 Antigens; D018984:Epitopes, T-Lymphocyte; D007166:Immunosuppressive Agents; D018996:Myelin P2 Protein; D010446:Peptide Fragments; D007371:Interferon-gamma