Volume 11 Supplement 1
Anti-CD3 monoclonal antibody as a possible therapeutic alternative in HAM/TSP
© Van Weyenbergh et al; licensee BioMed Central Ltd. 2014
Published: 7 January 2014
Anti-CD3 antibody therapy is used to treat transplant rejection and has been applied in several autoimmune diseases, such as type I diabetes and ulcerative colitis, but its potential in HAM/TSP has not been investigated. Therefore, we explored the effect of ex vivo treatment (24-96h) of PBMCs from HAM/TSP patients (n=15) and healthy controls (n=20, all from Salvador-Bahia, Brazil) with an anti-CD3 monoclonal antibody approved for in vivo treatment post-transplantation (produced under GMP conditions). In contrast to normal donors and patients in early disease stages, anti-CD3 treatment did not increase lymphoproliferation in PBMCs from advanced HAM/TSP patients (EDSS>4), but strongly induced apoptosis. In addition, anti-CD3 treatment did not induce a pro-inflammatory cytokine storm, either at the protein or mRNA level. Therefore, anti-CD3 treatment ex vivo might eliminate pathogenic T cells through activation-induced cell death. Since we have previously shown that pro-apoptotic capacity decreases over time in HAM/TSP patients, both defective (Fas-mediated) apoptosis and excessive lymphoproliferation, more pronounced in patients with advanced disease progression, can be restored by anti-CD3 treatment. Using microarray analysis, we found that treatment of HAM/TSP PBMCs with anti-CD3 mAb had a pronounced effect on gene expression, significantly (p<0.001) down-regulating 1918 genes (including pro-inflammatory genes) and up-regulating 1926 genes, including cell cycle-related and immunoregulatory genes, such as CTLA4. In conclusion, our results suggest anti-CD3 monoclonal antibody might be a possible therapeutic alternative in HAM/TSP, due to its immunomodulatory effect, by inducing apoptosis, reducing exacerbated lymphoproliferation and stimulating anti-inflammatory gene expression and/or proliferation of cells with immunoregulatory capacity.
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.