Immunological tolerance regulated by the interaction between T cell and antigen-presenting cell

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The presence of OX40^+ lymphocytes and OX40 ligand^+ (OX40L)^+ cells at the sites of inflammation in T cell-mediated disorders, such as autoimmunity, allergic and infectious diseases, and GVHD is well documented. These observations suggest important roles for OX40-OX40L interactions in immune disorders. CD25^+CD4^+ regulatory T (Treg) cells suppress autoinununity by controlling peripheral self-reactive T cell activation. Recently, several reports have revealed that OX40 is preferentially expressed on Treg cells in terms of mRNA and protein expression in mice. Thus we examined whether OX40-OX40L interaction may control Treg cell function that are essential for preventing autoimmunity.We found by using OX40L-deificient mice and mice overexpressing OX40L that CD25^-CD4^+ T cells became insensitive to Treg-mediated suppression when they were exposed to OX40L-expressing cells, or when they were treated with an agonistic OX40-specific monoclonal antibody. OX40 signaling could also abrogate the disease-preventing activity of Treg cells in an experimental model of inflammatory bowel disease using RAG2-deficient mice that expressed different levels of OX40L. Thus, these data show that OX40 signals can oppose Treg-mediated suppression when they are delivered directly to antigen-engaged naive T cells. Taken together, OX40 signaling directly control Treg-cell-mediated immune suppression.