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1996-03-04
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Document 0699
DOCN M9640699
TI Paradoxic effect of anti-CD4 therapy on lacrimal gland disease in
MRL/Mp-lpr/lpr mice.
DT 9604
AU Jabs DA; Burns WH; Prendergast RA; Department of Ophthalmology, Johns
Hopkins University School of; Medicine, Baltimore, Maryland, USA.
SO Invest Ophthalmol Vis Sci. 1996 Jan;37(1):246-50. Unique Identifier :
AIDSLINE MED/96142192
AB PURPOSE. MRL/Mp-lpr/lpr mice (MRL/lpr) spontaneously develop lacrimal
gland inflammatory lesions and are a model for the human disease
Sjogren'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-CD4 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 CD4+ 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.
DE Animal Antibodies, Monoclonal/ADMINISTRATION & DOSAGE/PHARMACOLOGY/
*THERAPEUTIC USE Antigens, CD4/*IMMUNOLOGY Autoantibodies Autoimmune
Diseases/IMMUNOLOGY/PATHOLOGY/*THERAPY CD4-Positive
T-Lymphocytes/*IMMUNOLOGY CD8-Positive T-Lymphocytes/*IMMUNOLOGY
Female Glomerulonephritis/IMMUNOLOGY/THERAPY Immunoenzyme Techniques
Injections, Intraperitoneal Lacrimal
Apparatus/IMMUNOLOGY/PATHOLOGY/VIROLOGY Lacrimal Apparatus
Diseases/IMMUNOLOGY/PATHOLOGY/*THERAPY Mice Mice, Mutant Strains
Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. JOURNAL ARTICLE
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).