K12/SECTM1, an interferon-γ regulated molecule, synergizes with CD28 to costimulate human T cell proliferation

K12/SECTM1 is induced by IFN‐γ in antigen‐presenting cells, and synergizes with anti‐CD28 antibody to costimulate CD4 and CD8 T cell proliferation and cytokine production. CD7 is a cell‐surface molecule, expressed on T lymphocytes and NK cells, which functions as a costimulatory receptor for T cell proliferation. SECTM1 has been proposed as a ligand for CD7. However, the expression pattern of this molecule in human immune cells and role in human T cell function remain unclear. In the present study, using human rSECTM1, we demonstrate that SECTM1 strongly costimulates CD4 and CD8 T cell proliferation and induces IFN‐γ production, likely via a CD7‐dependent mechanism. In addition, SECTM1 synergizes with suboptimal anti‐CD28 to strongly augment T cell functions. We found a robust induction of IL‐2 production when SECTM1 and anti‐CD28 signals were present with TCR ligation. Furthermore, addition of SECTM1 into a MLR significantly enhanced proliferation of alloantigen‐activated T cells, whereas blockade of SECTM1 inhibited T cell proliferation in a two‐way MLR assay. Simultaneously blocking the effect of SECTM1, along with CTLA‐4/Fc, diminishes two‐way MLR. Finally, we demonstrated that expression of SECTM1 is not detected in monocytes and imMoDCs at the protein level. However, it is strongly induced by IFN‐γ in monocytes and imMoDCs, and this induction is STAT1‐dependent. These results indicate that SECTM1 is a broadly expressed, IFN‐γ‐inducible molecule, which functions as a potent costimulatory ligand for T cell activation and is synergistic with anti‐CD28.