       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).

