Anti-CD4 monoclonal antibody therapy suppresses autoimmune disease in MRL/Mp-lpr/lpr mice

Douglas Jabs, C. Lynne Burek, Qile Hu, Rudolf C. Kuppers, Bella Lee, Robert A. Prendergast

Research output: Contribution to journalArticle

Abstract

MRL/Mp-lpr/lpr (MRL/lpr) mice spontaneously develop systemic autoimmune disease, characterized by vasculitis, lymphadenopathy, glomerulonephritis, and autoantibody formation. The target organ inflammatory lesions are composed largely of CD4+ "helper" T cells, while the massively enlarged lymph nodes are composed primarily of CD3+ CD4- CD8- TCR α β+ "double-negative" T cells. In this study we investigated the effect of treatment of MRL/lpr mice with antiCD4 monoclonal antibody (mAb); control groups consisted of animals treated with normal saline or rat immunoglobulin (Ig). Anti-CD4 mAb treatment, which was started at 4 weeks and continued through 20 weeks of age, resulted in a dramatic reduction of both the frequency and severity of the autoimmune disease, as demonstrated histologically and serologically. Anti-CD4 mAb therapy markedly reduced the frequency of glomerulonephritis and eliminated vasculitis of the major renal arterial branches. Glomerulonephritis was detected in 9 of 9 saline-treated, 9 of 9 rat Igtreated, but in only 1 of 9 anti-CD4 mAb-treated mice; vasculitis was detected in 6 of 9 salinetreated, 7 of 9 rat Ig-treated, but in none of 9 anti-CD4 mAb-treated mice. The frequency of antinuclear antibodies, titer of anti-dsDNA antibodies, and total Ig levels were all significantly reduced by anti-CD4 mAb therapy. These data support the hypothesis that CD4+ T cells play a central role in the disease process in this autoimmune strain.

Original languageEnglish (US)
Pages (from-to)496-507
Number of pages12
JournalCellular Immunology
Volume141
Issue number2
DOIs
StatePublished - 1992

Fingerprint

Autoimmune Diseases
Monoclonal Antibodies
Glomerulonephritis
Vasculitis
Immunoglobulins
Therapeutics
T-Lymphocytes
Antinuclear Antibodies
Helper-Inducer T-Lymphocytes
Autoantibodies
Anti-Idiotypic Antibodies
Lymph Nodes
Kidney
Control Groups

ASJC Scopus subject areas

  • Cell Biology
  • Immunology

Cite this

Anti-CD4 monoclonal antibody therapy suppresses autoimmune disease in MRL/Mp-lpr/lpr mice. / Jabs, Douglas; Burek, C. Lynne; Hu, Qile; Kuppers, Rudolf C.; Lee, Bella; Prendergast, Robert A.

In: Cellular Immunology, Vol. 141, No. 2, 1992, p. 496-507.

Research output: Contribution to journalArticle

Jabs, Douglas ; Burek, C. Lynne ; Hu, Qile ; Kuppers, Rudolf C. ; Lee, Bella ; Prendergast, Robert A. / Anti-CD4 monoclonal antibody therapy suppresses autoimmune disease in MRL/Mp-lpr/lpr mice. In: Cellular Immunology. 1992 ; Vol. 141, No. 2. pp. 496-507.
@article{492258c5d4fb4d108b372c7515f69fb3,
title = "Anti-CD4 monoclonal antibody therapy suppresses autoimmune disease in MRL/Mp-lpr/lpr mice",
abstract = "MRL/Mp-lpr/lpr (MRL/lpr) mice spontaneously develop systemic autoimmune disease, characterized by vasculitis, lymphadenopathy, glomerulonephritis, and autoantibody formation. The target organ inflammatory lesions are composed largely of CD4+ {"}helper{"} T cells, while the massively enlarged lymph nodes are composed primarily of CD3+ CD4- CD8- TCR α β+ {"}double-negative{"} T cells. In this study we investigated the effect of treatment of MRL/lpr mice with antiCD4 monoclonal antibody (mAb); control groups consisted of animals treated with normal saline or rat immunoglobulin (Ig). Anti-CD4 mAb treatment, which was started at 4 weeks and continued through 20 weeks of age, resulted in a dramatic reduction of both the frequency and severity of the autoimmune disease, as demonstrated histologically and serologically. Anti-CD4 mAb therapy markedly reduced the frequency of glomerulonephritis and eliminated vasculitis of the major renal arterial branches. Glomerulonephritis was detected in 9 of 9 saline-treated, 9 of 9 rat Igtreated, but in only 1 of 9 anti-CD4 mAb-treated mice; vasculitis was detected in 6 of 9 salinetreated, 7 of 9 rat Ig-treated, but in none of 9 anti-CD4 mAb-treated mice. The frequency of antinuclear antibodies, titer of anti-dsDNA antibodies, and total Ig levels were all significantly reduced by anti-CD4 mAb therapy. These data support the hypothesis that CD4+ T cells play a central role in the disease process in this autoimmune strain.",
author = "Douglas Jabs and Burek, {C. Lynne} and Qile Hu and Kuppers, {Rudolf C.} and Bella Lee and Prendergast, {Robert A.}",
year = "1992",
doi = "10.1016/0008-8749(92)90166-M",
language = "English (US)",
volume = "141",
pages = "496--507",
journal = "Cellular Immunology",
issn = "0008-8749",
publisher = "Academic Press Inc.",
number = "2",

}

TY - JOUR

T1 - Anti-CD4 monoclonal antibody therapy suppresses autoimmune disease in MRL/Mp-lpr/lpr mice

AU - Jabs, Douglas

AU - Burek, C. Lynne

AU - Hu, Qile

AU - Kuppers, Rudolf C.

AU - Lee, Bella

AU - Prendergast, Robert A.

PY - 1992

Y1 - 1992

N2 - MRL/Mp-lpr/lpr (MRL/lpr) mice spontaneously develop systemic autoimmune disease, characterized by vasculitis, lymphadenopathy, glomerulonephritis, and autoantibody formation. The target organ inflammatory lesions are composed largely of CD4+ "helper" T cells, while the massively enlarged lymph nodes are composed primarily of CD3+ CD4- CD8- TCR α β+ "double-negative" T cells. In this study we investigated the effect of treatment of MRL/lpr mice with antiCD4 monoclonal antibody (mAb); control groups consisted of animals treated with normal saline or rat immunoglobulin (Ig). Anti-CD4 mAb treatment, which was started at 4 weeks and continued through 20 weeks of age, resulted in a dramatic reduction of both the frequency and severity of the autoimmune disease, as demonstrated histologically and serologically. Anti-CD4 mAb therapy markedly reduced the frequency of glomerulonephritis and eliminated vasculitis of the major renal arterial branches. Glomerulonephritis was detected in 9 of 9 saline-treated, 9 of 9 rat Igtreated, but in only 1 of 9 anti-CD4 mAb-treated mice; vasculitis was detected in 6 of 9 salinetreated, 7 of 9 rat Ig-treated, but in none of 9 anti-CD4 mAb-treated mice. The frequency of antinuclear antibodies, titer of anti-dsDNA antibodies, and total Ig levels were all significantly reduced by anti-CD4 mAb therapy. These data support the hypothesis that CD4+ T cells play a central role in the disease process in this autoimmune strain.

AB - MRL/Mp-lpr/lpr (MRL/lpr) mice spontaneously develop systemic autoimmune disease, characterized by vasculitis, lymphadenopathy, glomerulonephritis, and autoantibody formation. The target organ inflammatory lesions are composed largely of CD4+ "helper" T cells, while the massively enlarged lymph nodes are composed primarily of CD3+ CD4- CD8- TCR α β+ "double-negative" T cells. In this study we investigated the effect of treatment of MRL/lpr mice with antiCD4 monoclonal antibody (mAb); control groups consisted of animals treated with normal saline or rat immunoglobulin (Ig). Anti-CD4 mAb treatment, which was started at 4 weeks and continued through 20 weeks of age, resulted in a dramatic reduction of both the frequency and severity of the autoimmune disease, as demonstrated histologically and serologically. Anti-CD4 mAb therapy markedly reduced the frequency of glomerulonephritis and eliminated vasculitis of the major renal arterial branches. Glomerulonephritis was detected in 9 of 9 saline-treated, 9 of 9 rat Igtreated, but in only 1 of 9 anti-CD4 mAb-treated mice; vasculitis was detected in 6 of 9 salinetreated, 7 of 9 rat Ig-treated, but in none of 9 anti-CD4 mAb-treated mice. The frequency of antinuclear antibodies, titer of anti-dsDNA antibodies, and total Ig levels were all significantly reduced by anti-CD4 mAb therapy. These data support the hypothesis that CD4+ T cells play a central role in the disease process in this autoimmune strain.

UR - http://www.scopus.com/inward/record.url?scp=0026637355&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0026637355&partnerID=8YFLogxK

U2 - 10.1016/0008-8749(92)90166-M

DO - 10.1016/0008-8749(92)90166-M

M3 - Article

C2 - 1576659

AN - SCOPUS:0026637355

VL - 141

SP - 496

EP - 507

JO - Cellular Immunology

JF - Cellular Immunology

SN - 0008-8749

IS - 2

ER -