An organic CD4 inhibitor reduces the clinical and pathological symptoms of acute experimental allergic encephalomyelitis.
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.
Edling
Andrea E
AE
Kimmel Cancer Institute, Jefferson Medical College, Philadelphia, PA 19107, USA.
Choksi
Swati
S
Huang
Ziwei
Z
Korngold
Robert
R
D000818:Animals; D015704:CD4 Antigens / Q000187:drug effects*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000209:etiology / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008822:Mice, Transgenic; D018991:Myelin Proteolipid Protein / Q000276:immunology; D009930:Organic Chemicals / Q000494:pharmacology*; D010446:Peptide Fragments / Q000276:immunology
D015704:CD4 Antigens; D007376:Interleukin-2; D018991:Myelin Proteolipid Protein; D009930:Organic Chemicals; D010446:Peptide Fragments; C407006:TJU 103; C435023:myelin proteolipid protein (139-151); D015847:Interleukin-4; D007371:Interferon-gamma