Paradoxic effect of anti-CD4 therapy on lacrimal gland disease in MRL/Mp-lpr/lpr mice

Douglas Jabs, William H. Burns, Robert A. Prendergast

Research output: Contribution to journalArticle

Abstract

Purpose. MRL/Mp-lpr/lpr mice (MRL/lpr) spontaneously develop lacrimal gland inflammatory lesions and are a model for the human disease Sjögren's syndrome. Therapy with monoclonal antibodies (mAb) to CD4 ameliorates the autoimmune renal, vasculitic, and intraocular inflammatory lesions in MRL/lpr mice. The effect of anti-CD4 mAb therapy on lacrimal gland immunopathology was evaluated. Methods. From 1 to 5 months of age, MRL/lpr mice were treated with weekly intraperitoneal injections of 2 mg anti-GD4 mAb, after which they were killed and their lacrimal glands were removed for histologic evaluation and immunocytochemistry. Control mice were administered weekly intraperitoneal injections of either saline or normal rat immunoglobulin. Results. Anti-CD4 mAb treatment produced no reduction in lacrimal gland inflammation but did change its morphology. In control mice, there were multiple sharply delineated foci of inflammatory cells in the lacrimal gland, whereas in anti-CD4 mAb-treated mice, there was a more diffuse inflammation surrounding ill-defined foci that spread throughout the gland. Immunocytochemistry revealed that in control mice, lesions were composed predominantly of CD44+ T cells, but in anti-CD4 mAb-treated mice, CD8+ T cells predominated. Conclusions. Although anti-CD4 mAb therapy of MRL/ lpr mice eliminated autoimmune renal disease, autoantibody formation, and ocular inflammatory disease, it had a paradoxic effect on lacrimal gland lesions. Lacrimal gland lesions in the anti-CD4 mAb-treated mice were not decreased, but they had a different morphology and a different immunocytochemical profile.

Original languageEnglish (US)
Pages (from-to)246-250
Number of pages5
JournalInvestigative Ophthalmology and Visual Science
Volume37
Issue number1
StatePublished - Jan 1 1996

Fingerprint

Lacrimal Apparatus
Monoclonal Antibodies
Therapeutics
Intraperitoneal Injections
Immunohistochemistry
Inbred MRL lpr Mouse
Inflammation
T-Lymphocytes
Kidney
Eye Diseases
Autoantibodies
Autoimmune Diseases
Immunoglobulins

Keywords

  • Autoimmune response
  • Immunopathology
  • Lacrimal gland
  • Monoclonal antibody therapy
  • Sjögren's syndrome

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

Paradoxic effect of anti-CD4 therapy on lacrimal gland disease in MRL/Mp-lpr/lpr mice. / Jabs, Douglas; Burns, William H.; Prendergast, Robert A.

In: Investigative Ophthalmology and Visual Science, Vol. 37, No. 1, 01.01.1996, p. 246-250.

Research output: Contribution to journalArticle

@article{ee06e931d133454dbdffe6abea9bdf13,
title = "Paradoxic effect of anti-CD4 therapy on lacrimal gland disease in MRL/Mp-lpr/lpr mice",
abstract = "Purpose. MRL/Mp-lpr/lpr mice (MRL/lpr) spontaneously develop lacrimal gland inflammatory lesions and are a model for the human disease Sj{\"o}gren's syndrome. Therapy with monoclonal antibodies (mAb) to CD4 ameliorates the autoimmune renal, vasculitic, and intraocular inflammatory lesions in MRL/lpr mice. The effect of anti-CD4 mAb therapy on lacrimal gland immunopathology was evaluated. Methods. From 1 to 5 months of age, MRL/lpr mice were treated with weekly intraperitoneal injections of 2 mg anti-GD4 mAb, after which they were killed and their lacrimal glands were removed for histologic evaluation and immunocytochemistry. Control mice were administered weekly intraperitoneal injections of either saline or normal rat immunoglobulin. Results. Anti-CD4 mAb treatment produced no reduction in lacrimal gland inflammation but did change its morphology. In control mice, there were multiple sharply delineated foci of inflammatory cells in the lacrimal gland, whereas in anti-CD4 mAb-treated mice, there was a more diffuse inflammation surrounding ill-defined foci that spread throughout the gland. Immunocytochemistry revealed that in control mice, lesions were composed predominantly of CD44+ T cells, but in anti-CD4 mAb-treated mice, CD8+ T cells predominated. Conclusions. Although anti-CD4 mAb therapy of MRL/ lpr mice eliminated autoimmune renal disease, autoantibody formation, and ocular inflammatory disease, it had a paradoxic effect on lacrimal gland lesions. Lacrimal gland lesions in the anti-CD4 mAb-treated mice were not decreased, but they had a different morphology and a different immunocytochemical profile.",
keywords = "Autoimmune response, Immunopathology, Lacrimal gland, Monoclonal antibody therapy, Sj{\"o}gren's syndrome",
author = "Douglas Jabs and Burns, {William H.} and Prendergast, {Robert A.}",
year = "1996",
month = "1",
day = "1",
language = "English (US)",
volume = "37",
pages = "246--250",
journal = "Investigative Ophthalmology and Visual Science",
issn = "0146-0404",
publisher = "Association for Research in Vision and Ophthalmology Inc.",
number = "1",

}

TY - JOUR

T1 - Paradoxic effect of anti-CD4 therapy on lacrimal gland disease in MRL/Mp-lpr/lpr mice

AU - Jabs, Douglas

AU - Burns, William H.

AU - Prendergast, Robert A.

PY - 1996/1/1

Y1 - 1996/1/1

N2 - Purpose. MRL/Mp-lpr/lpr mice (MRL/lpr) spontaneously develop lacrimal gland inflammatory lesions and are a model for the human disease Sjögren's syndrome. Therapy with monoclonal antibodies (mAb) to CD4 ameliorates the autoimmune renal, vasculitic, and intraocular inflammatory lesions in MRL/lpr mice. The effect of anti-CD4 mAb therapy on lacrimal gland immunopathology was evaluated. Methods. From 1 to 5 months of age, MRL/lpr mice were treated with weekly intraperitoneal injections of 2 mg anti-GD4 mAb, after which they were killed and their lacrimal glands were removed for histologic evaluation and immunocytochemistry. Control mice were administered weekly intraperitoneal injections of either saline or normal rat immunoglobulin. Results. Anti-CD4 mAb treatment produced no reduction in lacrimal gland inflammation but did change its morphology. In control mice, there were multiple sharply delineated foci of inflammatory cells in the lacrimal gland, whereas in anti-CD4 mAb-treated mice, there was a more diffuse inflammation surrounding ill-defined foci that spread throughout the gland. Immunocytochemistry revealed that in control mice, lesions were composed predominantly of CD44+ T cells, but in anti-CD4 mAb-treated mice, CD8+ T cells predominated. Conclusions. Although anti-CD4 mAb therapy of MRL/ lpr mice eliminated autoimmune renal disease, autoantibody formation, and ocular inflammatory disease, it had a paradoxic effect on lacrimal gland lesions. Lacrimal gland lesions in the anti-CD4 mAb-treated mice were not decreased, but they had a different morphology and a different immunocytochemical profile.

AB - Purpose. MRL/Mp-lpr/lpr mice (MRL/lpr) spontaneously develop lacrimal gland inflammatory lesions and are a model for the human disease Sjögren's syndrome. Therapy with monoclonal antibodies (mAb) to CD4 ameliorates the autoimmune renal, vasculitic, and intraocular inflammatory lesions in MRL/lpr mice. The effect of anti-CD4 mAb therapy on lacrimal gland immunopathology was evaluated. Methods. From 1 to 5 months of age, MRL/lpr mice were treated with weekly intraperitoneal injections of 2 mg anti-GD4 mAb, after which they were killed and their lacrimal glands were removed for histologic evaluation and immunocytochemistry. Control mice were administered weekly intraperitoneal injections of either saline or normal rat immunoglobulin. Results. Anti-CD4 mAb treatment produced no reduction in lacrimal gland inflammation but did change its morphology. In control mice, there were multiple sharply delineated foci of inflammatory cells in the lacrimal gland, whereas in anti-CD4 mAb-treated mice, there was a more diffuse inflammation surrounding ill-defined foci that spread throughout the gland. Immunocytochemistry revealed that in control mice, lesions were composed predominantly of CD44+ T cells, but in anti-CD4 mAb-treated mice, CD8+ T cells predominated. Conclusions. Although anti-CD4 mAb therapy of MRL/ lpr mice eliminated autoimmune renal disease, autoantibody formation, and ocular inflammatory disease, it had a paradoxic effect on lacrimal gland lesions. Lacrimal gland lesions in the anti-CD4 mAb-treated mice were not decreased, but they had a different morphology and a different immunocytochemical profile.

KW - Autoimmune response

KW - Immunopathology

KW - Lacrimal gland

KW - Monoclonal antibody therapy

KW - Sjögren's syndrome

UR - http://www.scopus.com/inward/record.url?scp=0030039547&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030039547&partnerID=8YFLogxK

M3 - Article

C2 - 8550330

AN - SCOPUS:0030039547

VL - 37

SP - 246

EP - 250

JO - Investigative Ophthalmology and Visual Science

JF - Investigative Ophthalmology and Visual Science

SN - 0146-0404

IS - 1

ER -