Jabs D A, Burns W H, Prendergast R A
Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Invest Ophthalmol Vis Sci. 1996 Jan;37(1):246-50.
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.
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.
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.
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.
MRL/Mp-lpr/lpr小鼠（MRL/lpr）可自发形成泪腺炎性病变，是人类干燥综合征的一种模型。用抗CD4单克隆抗体（mAb）治疗可改善MRL/lpr小鼠的自身免疫性肾、血管炎性和眼内炎性病变。评估了抗CD4 mAb治疗对泪腺免疫病理学的影响。
1至5月龄的MRL/lpr小鼠每周腹腔注射2 mg抗CD4 mAb进行治疗，之后处死小鼠并取出泪腺进行组织学评估和免疫细胞化学分析。对照小鼠每周腹腔注射生理盐水或正常大鼠免疫球蛋白。
抗CD4 mAb治疗并未减轻泪腺炎症，但改变了其形态。在对照小鼠中，泪腺有多个界限清晰的炎性细胞灶，而在抗CD4 mAb治疗的小鼠中，炎症更弥漫，围绕界限不清的病灶扩散至整个腺体。免疫细胞化学显示，对照小鼠的病变主要由CD4+ T细胞组成，但在抗CD4 mAb治疗的小鼠中，CD8+ T细胞占主导。
尽管用抗CD4 mAb治疗MRL/lpr小鼠消除了自身免疫性肾病、自身抗体形成和眼部炎性疾病，但对泪腺病变产生了矛盾的影响。抗CD4 mAb治疗的小鼠泪腺病变并未减轻，但形态和免疫细胞化学特征不同。
