Effects of early and late treatment with anti-CD4 monoclonal antibody on ocular lesions in MRL/Mp-lpr/lpr mice

The purpose of this study was to determine whether an early, short-course of anti-CD4 monoclonal antibody (mAb) therapy could prevent, or a late, short-course could reverse, the ocular inflammatory lesions in MRL/Mp- lpr/lpr mice. Groups of 12-14 mice were treated with one of four regimens: 1) anti-CD4 mAb from age 1-5 months (continuous treatment); 2) anti-CD4 antibody from 1-3 months (early treatment); 3) anti-CD4 antibody from 3-5 months (late treatment); and 4) control treatment. All injections were given as an initial single i.v. injection and an i.p. injection followed by weekly i.p. injections. Half the control mice received saline injections, and half received normal rat immunoglobulin. All animals were sacrificed at 5 months of age, and evaluated histologically for the presence of ocular inflammatory lesions. Splenic lymphocytes were evaluated for T-cell subset concentration by flow cytometry. Ocular inflammation was found in 31% of continuously- treated animals, 62% of early-treated, 92% of late-treated, and 86% of control-treated mice. Only continuous treatment significantly reduced the frequency of ocular lesions (p = 0.01) consistent with decreased CD4⁺ T cells throughout the course of the experiment. While continuous therapy with anti-CD4 mAb reduced the frequency of ocular inflammation in autoimmune MRL/Mp-lpr/lpr mice, the early treatment failed to abort the ocular disease, and late treatment failed to reverse ocular disease. These data strongly suggest that suppression of autoimmune ocular disease in this murine model is dependent on sustained reduction of CD4 cells.