PMID- 26924643 OWN - NLM STAT- MEDLINE DCOM- 20171201 LR - 20181113 IS - 1440-1711 (Electronic) IS - 0818-9641 (Linking) VI - 94 IP - 7 DP - 2016 Aug TI - Artificial antigen-presenting cells expressing HLA class II molecules as an effective tool for amplifying human specific memory CD4(+) T cells. PG - 662-72 LID - 10.1038/icb.2016.25 [doi] AB - Owing to their multiple immune functions, CD4(+) T cells are of major interest for immunotherapy in chronic viral infections and cancer, as well as for severe autoimmune diseases and transplantation. Therefore, standardized methods allowing rapid generation of a large number of CD4(+) T cells for adoptive immunotherapy are still awaited. We constructed stable artificial antigen-presenting cells (AAPCs) derived from mouse fibroblasts. They were genetically modified to express human leukocyte antigen (HLA)-DR molecules and the human accessory molecules B7.1, Intercellular adhesion molecule-1 (ICAM-1) and lymphocyte function-associated antigen-3 (LFA-3). AAPCs expressing HLA-DR1, HLA-DR15 or HLA-DR51 molecules and loaded with peptides derived from influenza hemagglutinin (HA), myelin basic protein (MBP) or factor VIII, respectively, activated specific CD4(+) T-cell clones more effectively than Epstein-Barr virus (EBV)-transformed B cells. We also showed that AAPCs were able to take up and process whole Ag proteins, and present epitopes to specific T cells. In primary cultures, AAPCs loaded with HA peptide allowed generation of specific Th1 lymphocytes from healthy donors as demonstrated by tetramer and intracellular cytokine staining. Although AAPCs were less effective than autologous peripheral blood mononuclear cells (PBMCs) to stimulate CD4(+) T cells in primary culture, AAPCs were more potent to reactivate and expand memory Th1 cells in a strictly Ag-dependent manner. As the availability of autologous APCs is limited, the AAPC system represents a stable and reliable tool to achieve clinically relevant numbers of CD4(+) T cells for adoptive immunotherapy. For fundamental research in immunology, AAPCs are also useful to decipher mechanisms involved in the development of human CD4 T-cell responses. FAU - Garnier, Anthony AU - Garnier A AD - Inserm U919, Serine Proteases and Pathophysiology of the Neurovascular Unit, Caen, France. AD - Universite de Caen Basse-Normandie, UFR Medecine, Caen, France. FAU - Hamieh, Mohamad AU - Hamieh M AD - Inserm U1079, Institute for Research and Innovation in Biomedicine (IRIB), Rouen University, Rouen, France. FAU - Drouet, Aurelie AU - Drouet A AD - Inserm U1079, Institute for Research and Innovation in Biomedicine (IRIB), Rouen University, Rouen, France. FAU - Leprince, Jerome AU - Leprince J AD - Inserm U982, Institute for Research and Innovation in Biomedicine (IRIB), Rouen University, Rouen, France. FAU - Vivien, Denis AU - Vivien D AD - Inserm U919, Serine Proteases and Pathophysiology of the Neurovascular Unit, Caen, France. AD - Universite de Caen Basse-Normandie, UFR Medecine, Caen, France. FAU - Frebourg, Thierry AU - Frebourg T AD - Inserm U1079, Institute for Research and Innovation in Biomedicine (IRIB), Rouen University, Rouen, France. AD - Department of Genetics, Rouen University Hospital, Rouen, France. FAU - Le Mauff, Brigitte AU - Le Mauff B AD - Inserm U919, Serine Proteases and Pathophysiology of the Neurovascular Unit, Caen, France. AD - Universite de Caen Basse-Normandie, UFR Medecine, Caen, France. AD - CHU Caen, Department of Immunology and Immunopathology, Caen, France. AD - Etablissement Francais du Sang, Normandie, Caen, France. FAU - Latouche, Jean-Baptiste AU - Latouche JB AD - Inserm U1079, Institute for Research and Innovation in Biomedicine (IRIB), Rouen University, Rouen, France. AD - Department of Genetics, Rouen University Hospital, Rouen, France. FAU - Toutirais, Olivier AU - Toutirais O AD - Inserm U919, Serine Proteases and Pathophysiology of the Neurovascular Unit, Caen, France. AD - Universite de Caen Basse-Normandie, UFR Medecine, Caen, France. AD - CHU Caen, Department of Immunology and Immunopathology, Caen, France. AD - Etablissement Francais du Sang, Normandie, Caen, France. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20160229 PL - United States TA - Immunol Cell Biol JT - Immunology and cell biology JID - 8706300 RN - 0 (Epitopes) RN - 0 (Histocompatibility Antigens Class II) RN - 0 (Peptides) SB - IM MH - Animals MH - Antigen Presentation/immunology MH - Antigen-Presenting Cells/*immunology MH - Artificial Cells/*immunology MH - CD4-Positive T-Lymphocytes/cytology/*immunology MH - Cell Proliferation MH - Epitopes/immunology MH - Histocompatibility Antigens Class II/*metabolism MH - Humans MH - *Immunologic Memory MH - Lymphocyte Activation/immunology MH - Mice MH - NIH 3T3 Cells MH - Peptides/metabolism MH - Phenotype MH - Tissue Donors EDAT- 2016/03/01 06:00 MHDA- 2017/12/02 06:00 CRDT- 2016/03/01 06:00 PHST- 2015/10/13 00:00 [received] PHST- 2016/02/21 00:00 [revised] PHST- 2016/02/22 00:00 [accepted] PHST- 2016/03/01 06:00 [entrez] PHST- 2016/03/01 06:00 [pubmed] PHST- 2017/12/02 06:00 [medline] AID - icb201625 [pii] AID - 10.1038/icb.2016.25 [doi] PST - ppublish SO - Immunol Cell Biol. 2016 Aug;94(7):662-72. doi: 10.1038/icb.2016.25. Epub 2016 Feb 29.