An organic CD4 inhibitor reduces the clinical and pathological symptoms of acute experimental allergic encephalomyelitis

Journal of Autoimmunity
A E EdlingR Korngold

Abstract

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.

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Citations

Aug 4, 2004·Current Opinion in Chemical Biology·Len PagliaroSteven Butcher
Apr 25, 2006·Biochemical and Biophysical Research Communications·Gail H MarracciDennis N Bourdette
Dec 11, 2003·Multiple Sclerosis : Clinical and Laboratory Research·Shunya NakaneNoritoshi Shibuya
Jan 10, 2012·Bioorganic & Medicinal Chemistry·Young Ho JeonSunghoon Kim
Dec 30, 2021·CNS Neuroscience & Therapeutics·Hongsheng XieZhiyun Jia

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