Anti-CD44 treatment does not prevent the extravasation of autopathogenic T cells to the thyroid in experimental autoimmune thyroiditis.
The hyaluronic acid binding glycoprotein CD44 is expressed on a wide variety of cells, and by mediating interactions between cells and extracellular matrices promotes the movement of cells from the circulation into organs. Recent reports have described the effects of an antibody specific for CD44 (IM7) that has beneficial effects in two murine models of autoimmune disease. Both experimental allergic encephalomyelitis (EAE) and collagen-induced arthritis were ameliorated by treatment with IM7, which was considered to be acting by preventing the homing of lymphocytes to the relevant inflammatory sites, namely the central nervous system and the synovium, respectively. In this study the same anti-CD44 antibody was used to try to prevent leucocytic infiltration of the thyroid in the murine model of Hashimoto's thyroiditis, experimental autoimmune thyroiditis (EAT). We report that, in contrast to the previous findings, this antibody had an exacerbating effect on thyroiditis induced by immunization of mice with mouse thyroglobulin (MTg) and complete Freund's adjuvant (CFA). Thyroid infiltrates lasted longer and showed increased severity compared with untreated or control antibody-treated mice. Antibody responses to MTg were unaffected by antibody treatment. The data suggest that simple rules cannot be drawn that predict the potential broad therapeutic use of anti-CD44 reagents, presumably due to differences in the cellular phenotypes and the dynamics of their movement into inflammatory sites during different disease processes.
Parish
N M
NM
Division of Immunology, Department of Pathology, University of Cambridge, Cambridge, UK.
Brennan
F R
FR
Cooke
A
A
D000818:Animals; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D001323:Autoantibodies / Q000097:blood; D002455:Cell Division / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D005260:Female; D018960:Hyaluronan Receptors / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D008808:Mice, Inbred CBA; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D013954:Thyroglobulin / Q000276:immunology; D013961:Thyroid Gland / Q000276:immunology*; D013967:Thyroiditis, Autoimmune / Q000276:immunology*
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D018960:Hyaluronan Receptors; D013954:Thyroglobulin