J Autoimmun 2002 Mar;18(2):169-79
Edling AE, Choksi S, Huang Z, Korngold R.
Kimmel Cancer Institute, Jefferson Medical College, Philadelphia, PA
CD4(+) T cells have an important role in mediating the pathogenesis of many human and experimental autoimmune diseases including experimental allergic encephalomyelitis (EAE), a demyelinating animal model for multiple sclerosis (MS).
We applied a computer screening approach to select a small organic molecule, TJU103, that would specifically inhibit autoreactive CD4(+) T cells by disrupting the function of the CD4 molecule during activation.
Upon studying the therapeutic effect of TJU103 in acute EAE, it was found that administration shortly before or after the onset of clinical symptoms reduced the severity of disease in both SJL and SWXJ-14 mouse models.
In addition, TJU103 treatment could affect both in vivo responses to EAE rechallenge and secondary in vitro proliferation and cytokine production of T cells responding to proteolipid protein epitope 139-151 (PLPe).
These results demonstrate the potential of the TJU103 organic inhibitor
for future clinical application in CD4(+) T cell-mediated diseases.
Copyright 2002 Elsevier Science Ltd.