Paradoxic effect of anti-CD4 therapy on lacrimal gland disease in MRL/Mp-lpr/lpr mice.
OBJECTIVE
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-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.
Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
D A
DA
Jabs
W H
WH
Burns
R A
RA
Prendergast
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001323:Autoantibodies; D001327:Autoimmune Diseases / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D015704:CD4 Antigens / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D005921:Glomerulonephritis / Q000276:immunology / Q000628:therapy; D007124:Immunoenzyme Techniques; D007274:Injections, Intraperitoneal; D007765:Lacrimal Apparatus / Q000276:immunology / Q000473:pathology / Q000821:virology; D007766:Lacrimal Apparatus Diseases / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008817:Mice, Mutant Strains
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D015704:CD4 Antigens