title: K12/SECTM1, an interferon-γ regulated molecule, synergizes with CD28 to costimulate human T cell proliferation.
abstract: 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.
authors.affiliation: Molecular and Cellular Oncogenesis Program, The Wistar Institute, 3601 Spruce St., Philadelphia, PA 19104, USA. twang@wistar.org
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.forename: Catherine
authors.initials: C
authors.lastname: Huang
authors.forename: Alfonso
authors.initials: A
authors.lastname: Lopez-Coral
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Slentz-Kesler
authors.forename: Min
authors.initials: M
authors.lastname: Xiao
authors.forename: E John
authors.initials: EJ
authors.lastname: Wherry
authors.forename: Russel E
authors.initials: RE
authors.lastname: Kaufman
mesh_terms: D019011:Antigens, CD7 / Q000378:metabolism; D001483:Base Sequence; D018106:CD28 Antigens / Q000276:immunology / Q000378:metabolism*; D060908:CTLA-4 Antigen / Q000378:metabolism; D020869:Gene Expression Profiling; D057809:HEK293 Cells; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology; D019169:Jurkat Cells; D008024:Ligands; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D059372:Nucleotide Motifs; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000032:analysis; D050794:STAT1 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*
chemical_list: D019011:Antigens, CD7; D018106:CD28 Antigens; D060908:CTLA-4 Antigen; D007141:Immunoglobulin Fc Fragments; D008024:Ligands; D008565:Membrane Proteins; D012333:RNA, Messenger; C111200:SECTM1 protein, human; D050794:STAT1 Transcription Factor; D007371:Interferon-gamma