Opposing effects of CTLA4-Ig and anti-CD80 (B7-1) plus anti-CD86 (B7-2) on experimental allergic encephalomyelitis

Peter J. Perrin; Dorothy Scott; Tiffany A. Davis; Gary S. Gray; Michael J. Doggett; Ryo Abe; Carl H. June; Michael K. Racke; Thomas Davis

doi:10.1016/0165-5728(95)00172-7

Opposing effects of CTLA4-Ig and anti-CD80 (B7-1) plus anti-CD86 (B7-2) on experimental allergic encephalomyelitis

Peter J. Perrin^*, Dorothy Scott, Tiffany A. Davis, Gary S. Gray, Michael J. Doggett, Ryo Abe, Carl H. June, Michael K. Racke, Thomas Davis

^*Corresponding author for this work

Navy Medical Research Center (NMRC)

Research output: Contribution to journal › Article › peer-review

42 Scopus citations

Abstract

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)-γ and interleukin (IL)-2 producing cells, but a dramatic increase in tumor necrosis factor (TNF)-α 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.

Original language	English
Pages (from-to)	31-39
Number of pages	9
Journal	Journal of Neuroimmunology
Volume	65
Issue number	1
DOIs	https://doi.org/10.1016/0165-5728(95)00172-7
State	Published - Mar 1996

Keywords

B7 receptors
CD80
CD86
CTLA-4
Experimental allergic encephalomyelitis
Interferon-γ
Interleukin-10
Interleukin-2
Tumor necrosis factor-

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@article{726dc60a96e348e8b58c28484e08b688,

title = "Opposing effects of CTLA4-Ig and anti-CD80 (B7-1) plus anti-CD86 (B7-2) on experimental allergic encephalomyelitis",

abstract = "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)-γ and interleukin (IL)-2 producing cells, but a dramatic increase in tumor necrosis factor (TNF)-α 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.",

keywords = "B7 receptors, CD80, CD86, CTLA-4, Experimental allergic encephalomyelitis, Interferon-γ, Interleukin-10, Interleukin-2, Tumor necrosis factor-",

author = "Perrin, {Peter J.} and Dorothy Scott and Davis, {Tiffany A.} and Gray, {Gary S.} and Doggett, {Michael J.} and Ryo Abe and June, {Carl H.} and Racke, {Michael K.} and Thomas Davis",

year = "1996",

month = mar,

doi = "10.1016/0165-5728(95)00172-7",

language = "English",

volume = "65",

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AU - Perrin, Peter J.

AU - Scott, Dorothy

AU - Davis, Tiffany A.

AU - Gray, Gary S.

AU - Doggett, Michael J.

AU - Abe, Ryo

AU - June, Carl H.

AU - Racke, Michael K.

AU - Davis, Thomas

PY - 1996/3

Y1 - 1996/3

N2 - 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)-γ and interleukin (IL)-2 producing cells, but a dramatic increase in tumor necrosis factor (TNF)-α 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.

AB - 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)-γ and interleukin (IL)-2 producing cells, but a dramatic increase in tumor necrosis factor (TNF)-α 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.

KW - B7 receptors

KW - CD80

KW - CD86

KW - CTLA-4

KW - Experimental allergic encephalomyelitis

KW - Interferon-γ

KW - Interleukin-10

KW - Interleukin-2

KW - Tumor necrosis factor-

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AN - SCOPUS:0029921933

SN - 0165-5728

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IS - 1

ER -

Opposing effects of CTLA4-Ig and anti-CD80 (B7-1) plus anti-CD86 (B7-2) on experimental allergic encephalomyelitis

Abstract

Keywords

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