title: HCMV-specific T-cell therapy: do not forget supply of help.
abstract: Human cytomegalovirus infections have a major negative effect on morbidity and mortality of immunosuppressed allograft recipients and indirectly on graft function and survival. The adoptive antiviral T-cell therapy is a novel therapeutic tool to restore immune competence after solid organ transplantation. Till now, the antiviral T-cell products mainly focused on cytotoxic CD8(+) T cells, whereas CD4(+) T cells played a minor role. Here, we demonstrate the importance of CD4(+) T cells within T-cell lines specific for human cytomegalovirus besides its essential support for the quality of CD8(+) T-cell memory. Virus-specific CD4(+) T cells elicit profound functionality after rechallenge (multicytokine secretors, CD137, CD154, and CD107a expression and killing of infected target cells). The CD4(+) T cells show predominantly a Th1 phenotype with cytolytic properties that is mainly perforin-dependent. The data demonstrate the significance of CD4(+) T cells within T-cell products to achieve a successful adoption with enhanced efficacy.
authors: Institute of Medical Immunology, Charité Universitätsmedizin Berlin, Berlin, Germany.
authors: Ben
authors: B
authors: Hammoud
authors: Michael
authors: M
authors: Schmueck
authors: Annika M
authors: AM
authors: Fischer
authors: Henrike
authors: H
authors: Fuehrer
authors: Su-Jin
authors: SJ
authors: Park
authors: Levent
authors: L
authors: Akyuez
authors: Joerg C
authors: JC
authors: Schefold
authors: Martin J
authors: MJ
authors: Raftery
authors: Günther
authors: G
authors: Schönrich
authors: Andreas M
authors: AM
authors: Kaufmann
authors: Hans-Dieter
authors: HD
authors: Volk
authors: Petra
authors: P
authors: Reinke
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D023201:CD40 Ligand / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000637:transplantation; D064987:Cell- and Tissue-Based Therapy; D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000276:immunology* / Q000628:therapy* / Q000821:virology; D006801:Humans; D016219:Immunotherapy, Adoptive; D052118:Lysosomal-Associated Membrane Protein 1 / Q000378:metabolism; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9 / Q000378:metabolism
chemical_list: D052118:Lysosomal-Associated Membrane Protein 1; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9; D023201:CD40 Ligand