Systemically Circulating Colitogenic Memory CD4⁺T Cells May Be an Ideal Target for the Treatment of Inflammatory Bowel Diseases

Abstract

Inflammatory bowel diseases (IBD) are thought to be caused by a complex interaction of genetic, immunological, and environmental factors. Why is it that once an IBD develops it lasts a long time? Considering this simple question, we propose that coliotogenic memory CD4⁺T cells that remember the prototype of the disease in each patient are formed in IBD at the onset, and, perceiving them as “benign T-cell leukemia”-like lifelong memory CD4⁺T cells that hematogenously spread throughout the body, we thus propose that systemic circulating colitogenic memory CD4⁺T cells would be an ideal target for the treatment of IBD. Accordingly, selective depletion of colitogenic memory CD4⁺T cells by leukocytapheresis and blockade of circulation of colitogenic memory CD4⁺T cells by a newly developed immunosuppressant, FTY720, may be associated with dramatic efficacy and a marked reduction of inflammatory cytokines produced by activated leucocytes. We here describe the immunological pathogenesis focusing on the generation of circulating colitogenic memory CD4⁺T cells and the possible logics of leukocytapheresis and FTY720 for the treatment of IBD.