Anti-CD5 therapy decreases severity of established disease in collagen type II-induced arthritis in DBA/1 mice

Abstract

SUMMARYCollagen-induced arthritis has been widely used as an animal model of rheumatoid arthritis. We have used this model with a view to determining potential therapeutic targets for the treatment of human disease. To do this we have attempted to modulale the progression of established arthritis over a 10-day time period following the first appearance of disease, by i.p. injection of one of three different MoAbs. These eonsist of a rat IgG2a specific for the CD5 antigen expressed on all T cells and a subpopulation of B eells, a mouse IgG2b recognizing the CD72 antigen, and a rat IgM speeifie for the B220 molecule, CD72 and B220 both being expressed on all B cells. None of the three MoAbs had depleting activity in vivo. The progression of arthritis was monitored both clinically, and histologically. The effects of treatment with anti-CD5 and anti-CD72 antibodies were compared with control antibodies ofthe same species class and subclass. In the case of anti-B220 antibodies, the effects of treatment were eompared with administration of FBS. Of these MoAbs, only treatment with anti-CD5 resulted in disease amelioration with significant decrease in disease severity in 60% of the animals. These changes became apparent 6 days after initiation of treatment. There were no significant differences in serum levels of IgG antibodies to native bovine collagen type II between the groups of treated and control mice. Possible meehanisms underlying the modification of disease expression following treatment with anti-CD5 MoAb are discussed.

Effects of Peptide-Induced Immune Tolerance on Murine Lupus

“…This is a significant finding and the next step will be to decipher the mechanisms with future functional studies including testing B cells from anti-CD5 treated control mice. In agreement with our experiments, a previous study showed that anti-CD5 therapy decreases severity of established disease in collagen-induced arthritis in DBA/1 mice ( 81 ). Thus, our data with pCons therapy has clinical and therapeutic relevance in peptide induced immune tolerance.…”

The Conserved Scavenger Receptor Cysteine-Rich Superfamily in Therapy and Diagnosis

“…Studies with animal models have also shown that treatment with monoclonal anti-CD5 antibodies can indeed improve disease score and decrease severity of autoimmune disorders: this has been described for collagen-induced arthritis in mice (Plater-Zyberk et al, 1994) and also for mesangioproliferative glomerulonephritis in rats (Ikezumi et al, 2000). Translation of these results into the clinic, however, has met with mixed success: although preliminary studies had shown encouraging safety and activity profiles for an immunoconjugate of ricin A chain and anti-CD5 monoclonal antibody in rheumatoid arthritis (Strand et al, 1993;Fishwild and Strand 1994), a later, double-blind, placebo-controlled study failed to find a significant decrease in disease severity for the immunoconjugate-treated patients (Olsen et al, 1996).…”

Co-stimulation and T cells as therapeutic targets

“…Anti-CD5 antibody treatment had a partial therapeutic effect in CIA in DBA/1 mice (57). When an anti-CD5 antibody was covalently linked to the A chain of ricin, binding was followed by internalization and intracellular toxin release.…”