title: TIRC7 inhibits T cell proliferation by modulation of CTLA-4 expression.
abstract: Ab targeting of TIRC7 has been shown previously to inhibit T cell proliferation and Th1 lymphocyte-associated cytokine production. In this study, we demonstrate that Ab targeting of TIRC7 induces early cell surface expression of CTLA-4. The majority of stimulated CD4+ and CD8+ human T cells coexpress CTLA-4 and TIRC7. Similar to CTLA-4, TIRC7 rapidly accumulates at the site of Ag adhesion upon T cell activation. TIRC7 seems to colocalize with CTLA-4 in human T cells, and both molecules are associated with clathrin-coated vesicles, indicating they share intracellular transport systems. Moreover, Ab targeting of TIRC7 results in an early activation of CTLA-4 transcription. The inhibition of cell proliferation mediated by TIRC7 is dependent on CTLA-4 expression because the TIRC7-mediated inhibitory effects on cell proliferation and cytokine expression are abolished by Ab blockade of CTLA-4. Splenocytes obtained from CTLA-4-deficient mice are not responsive to TIRC7 Ab targeting. Thus, TIRC7 acts as an upstream regulatory molecule of CTLA-4 expression.
authors.affiliation: Institut für Medizinische Immunologie, Campus Charité Mitte, Humboldt-Universität zu Berlin, Berlin, Germany.
authors.forename: Grit-Carsta
authors.initials: GC
authors.lastname: Bulwin
authors.forename: Thomas
authors.initials: T
authors.lastname: Heinemann
authors.forename: Volker
authors.initials: V
authors.lastname: Bugge
authors.forename: Michael
authors.initials: M
authors.lastname: Winter
authors.forename: Anke
authors.initials: A
authors.lastname: Lohan
authors.forename: Mirko
authors.initials: M
authors.lastname: Schlawinsky
authors.forename: Anke
authors.initials: A
authors.lastname: Schulze
authors.forename: Stephanie
authors.initials: S
authors.lastname: Wälter
authors.forename: Robert
authors.initials: R
authors.lastname: Sabat
authors.forename: Ralf
authors.initials: R
authors.lastname: Schülein
authors.forename: Burkhard
authors.initials: B
authors.lastname: Wiesner
authors.forename: Rüdiger W
authors.initials: RW
authors.lastname: Veh
authors.forename: Jürgen
authors.initials: J
authors.lastname: Löhler
authors.forename: Richard S
authors.initials: RS
authors.lastname: Blumberg
authors.forename: Hans-Dieter
authors.initials: HD
authors.lastname: Volk
authors.forename: Nalân
authors.initials: N
authors.lastname: Utku
mesh_terms: D019138:Antibodies, Blocking / Q000494:pharmacology; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D015703:Antigens, CD / Q000096:biosynthesis* / Q000276:immunology / Q000502:physiology; D000943:Antigens, Differentiation / Q000096:biosynthesis* / Q000276:immunology / Q000502:physiology; D001665:Binding Sites / Q000276:immunology; D060908:CTLA-4 Antigen; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D022163:Clathrin-Coated Vesicles / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D006131:Growth Inhibitors / Q000502:physiology*; D006801:Humans; D007106:Immune Sera / Q000494:pharmacology; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007424:Intracellular Fluid / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D008565:Membrane Proteins / Q000276:immunology / Q000378:metabolism; D021381:Protein Transport / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D015854:Up-Regulation / Q000276:immunology; D025262:Vacuolar Proton-Translocating ATPases / Q000276:immunology / Q000378:metabolism / Q000502:physiology*
chemical_list: D019138:Antibodies, Blocking; D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C556707:Ctla4 protein, mouse; D016207:Cytokines; D006131:Growth Inhibitors; D007106:Immune Sera; D007166:Immunosuppressive Agents; D008565:Membrane Proteins; C472421:TCIRG1 protein, human; D025262:Vacuolar Proton-Translocating ATPases