Role of T cells in the pathogenesis of autoimmune lacrimal gland disease in MRL/Mp-lpr/lpr mice.
OBJECTIVE
MRL/Mp-lpr/lpr mice (MRL/lpr) spontaneously develop an autoimmune disease, including lacrimal gland lesions, which are a model for Sjögren's syndrome. Target organ lesions in MRL/lpr mice are composed largely of CD4+ T cells, and treatment with monoclonal antibodies (mAb) against CD4 improves in the systemic autoimmune disease but not the lacrimal gland inflammation. In anti-CD4 mAb-treated MRL/lpr mice, the lacrimal gland lesions are composed largely of CD8+ T cells. The effects of depletion of: (1) all T cells; (2) both CD4+ and CD8+ T cells, and (3) only CD8+ T cells on the lacrimal gland disease were investigated.


METHODS
MRL/lpr mice underwent neonatal thymectomy and were treated with weekly injections of 6 mg of anti-Thy 1 mAb from age one week until sacrifice at age five months. Control nonthymectomized mice underwent similar treatment with either saline or normal rat immunoglobulin (rIg) injections. In a second experiment, MRL/lpr mice were treated with weekly injections of either: (1) 2 mg anti-CD4 mAb and 5 mg anti-CD8; or (2) 5 mg anti-CD8 alone. Control mice underwent similar treatment with either saline or rIg injections.


RESULTS
Combined treatment with neonatal thymectomy and anti-Thy 1 mAb was effective in reducing the lacrimal gland disease in both frequency (50% > or = grade 3 vs. 100% in controls, P < 0.002) and extent (median 0% of lacrimal gland area involved by inflammation vs. 14.8% in controls; P = 0.01). Combined anti-CD4 and anti-CD8 therapy also was effective in reducing the lacrimal gland disease in terms of frequency (25% grade 3 vs. 93% in controls; P = 0.002) and extent (median 0% of lacrimal gland involved by inflammation vs. 12.9% in controls; P = 0.0005). Treatment with anti-CD8 mAb therapy alone was ineffective. The systemic autoimmune disease was also improved by T cell depletion and by combined anti-CD4 and anti-CD8 mAb therapy but not by anti-CD8 mAb therapy alone.


CONCLUSIONS
Suppression of both CD4+ and CD8+ T cells is required to suppress lacrimal gland inflammation in MRL/lpr mice.
Jabs
D A
DA
Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Lee
B
B
Prendergast
R A
RA
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D001327:Autoimmune Diseases / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D005123:Eye / Q000473:pathology; D007518:Isoantibodies / Q000494:pharmacology; D007668:Kidney / Q000473:pathology; D007765:Lacrimal Apparatus / Q000473:pathology; D007766:Lacrimal Apparatus Diseases / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control; D018655:Lymphocyte Count / Q000187:drug effects; D051379:Mice; D019463:Mice, Inbred MRL lpr; D016513:Mice, SCID; D051381:Rats; D013601:T-Lymphocytes / Q000473:pathology / Q000502:physiology*; D013934:Thymectomy
D000911:Antibodies, Monoclonal; D007518:Isoantibodies; C035678:anti-Thy antibody