Opposing effects of CTLA4-Ig and anti-CD80 (B7-1) plus anti-CD86 (B7-2) on experimental allergic encephalomyelitis.
The roles of the B7 receptors, CD80 and CD86, during actively induced experimental allergic encephalomyelitis were examined with specific monoclonal antibodies and CTLA4-Ig. Injection of CTLA4-Ig on day 2 post-immunization resulted in decreased incidence and severity of resultant disease. Anti-CD80 injection on day 2 blocked development of the first disease episode. Subsequent relapses were unaffected. In contrast, injection of anti-CD86 alone had no effect. Surprisingly, combined anti-CD80 + anti-CD86 monoclonal antibody injection on day 2 resulted in marked exacerbation of disease. Examination of cytokine production in the draining lymph node cells demonstrated a reduction in both interferon (IFN)-gamma and interleukin (IL)-2 producing cells, but a dramatic increase in tumor necrosis factor (TNF)-alpha secretion in animals receiving both monoclonal antibodies. These results suggest distinct roles for CD80 and CD86 in the initiation of EAE, resulting in the diverse clinical outcomes observed in this model of EAE.
Perrin
P J
PJ
Immune Cell Biology Program, Naval Medical Research Institute, Bethesda, MD 20889-5607, USA. rinOpjp@bumed30.navy.med.mil
Scott
D
D
Davis
T A
TA
Gray
G S
GS
Doggett
M J
MJ
Abe
R
R
June
C H
CH
Racke
M K
MK
D000069594:Abatacept; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD / Q000276:immunology*; D000943:Antigens, Differentiation / Q000494:pharmacology*; D018122:B7-1 Antigen / Q000276:immunology*; D051940:B7-2 Antigen; D060908:CTLA-4 Antigen; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000517:prevention & control; D005260:Female; D006168:Guinea Pigs; D007114:Immunization; D018796:Immunoconjugates; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D007376:Interleukin-2 / Q000276:immunology / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains; D004676:Myelin Basic Protein / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism; D010566:Virulence Factors, Bordetella / Q000276:immunology
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D060908:CTLA-4 Antigen; C497965:Cd86 protein, mouse; C556707:Ctla4 protein, mouse; D018796:Immunoconjugates; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D008562:Membrane Glycoproteins; D004676:Myelin Basic Protein; D014409:Tumor Necrosis Factor-alpha; D010566:Virulence Factors, Bordetella; D000069594:Abatacept; D007371:Interferon-gamma