Myeloid-derived suppressor cells expressing a self-antigen ameliorate experimental autoimmune encephalomyelitis.
Previous work by our group showed that transferring bone marrow cells transduced with a self-antigen induced immune tolerance and ameliorated experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis (MS). We also found that following retroviral transduction of murine bone marrow (BM) cells, the majority of cells generated and transduced were myeloid-derived suppressor cells (MDSCs). Here, we aimed to determine whether purified antigen-expressing MDSCs have similar therapeutic effects than those of unfractionated BM, and to investigate their potential mechanisms. We performed phenotypic and functional analyses in these cells using the same animal model, and we used purified antigen-expressing MDSCs in preventive and therapeutic approaches. These cells exerted therapeutic effects similar to those of BM cells, which depended upon self-antigen expression. The majority of monocytic (M)-MDSCs expressed the immunosuppressive molecule programmed death ligand-1 (PD-L1), CD80, CD86 and MHC class II molecules. Additionally, the animals infused with antigen-expressing cells exhibited lower percentages of activated T cells and higher percentages of B cells with a regulatory phenotype (B220+CD1dhighCD5+) in the spleen than their respective controls. MDSCs expressing self-antigens, alloantigens or therapeutic transgenes are tolerogenic and can be exploited therapeutically in autoimmune diseases, transplantation and in gene therapy, respectively.
Gene and Cell Therapy Laboratory, Vall d'Hebron Institut de Recerca (VHIR), Passeig Vall d'Hebron 119-129, Barcelona 08035, Spain; Universitat Autònoma de Barcelona, 08193, Bellaterra, Cerdanyola del Vallès, Spain. Electronic address: silvia.casacuberta@vhir.org.
Silvia
S
Casacuberta-Serra
Universitat Autònoma de Barcelona, 08193, Bellaterra, Cerdanyola del Vallès, Spain; Servei de Neurologia-Neuroimmunologia Clínica, Centre d'Esclerosi Múltiple de Catalunya (Cemcat), VHIR, Hospital Universitari Vall d'Hebron, Passeig Vall d'Hebron 119-129, Barcelona 08035, Spain. Electronic address: carme.costa@vhir.org.
Carme
C
Costa
Universitat Autònoma de Barcelona, 08193, Bellaterra, Cerdanyola del Vallès, Spain; Servei de Neurologia-Neuroimmunologia Clínica, Centre d'Esclerosi Múltiple de Catalunya (Cemcat), VHIR, Hospital Universitari Vall d'Hebron, Passeig Vall d'Hebron 119-129, Barcelona 08035, Spain. Electronic address: herena.eixarch@vhir.org.
Herena
H
Eixarch
Gene and Cell Therapy Laboratory, Vall d'Hebron Institut de Recerca (VHIR), Passeig Vall d'Hebron 119-129, Barcelona 08035, Spain; Universitat Autònoma de Barcelona, 08193, Bellaterra, Cerdanyola del Vallès, Spain. Electronic address: mjosemansilla@yahoo.es.
María José
MJ
Mansilla
Gene and Cell Therapy Laboratory, Vall d'Hebron Institut de Recerca (VHIR), Passeig Vall d'Hebron 119-129, Barcelona 08035, Spain; Universitat Autònoma de Barcelona, 08193, Bellaterra, Cerdanyola del Vallès, Spain. Electronic address: sergio.lopez.estevez@gmail.com.
Sergio
S
López-Estévez
Gene and Cell Therapy Laboratory, Vall d'Hebron Institut de Recerca (VHIR), Passeig Vall d'Hebron 119-129, Barcelona 08035, Spain; Universitat Autònoma de Barcelona, 08193, Bellaterra, Cerdanyola del Vallès, Spain. Electronic address: lmartorc@gmail.com.
Lluís
L
Martorell
Gene and Cell Therapy Laboratory, Vall d'Hebron Institut de Recerca (VHIR), Passeig Vall d'Hebron 119-129, Barcelona 08035, Spain; Universitat Autònoma de Barcelona, 08193, Bellaterra, Cerdanyola del Vallès, Spain. Electronic address: marta.pares@vhir.org.
Marta
M
Parés
Universitat Autònoma de Barcelona, 08193, Bellaterra, Cerdanyola del Vallès, Spain; Servei de Neurologia-Neuroimmunologia Clínica, Centre d'Esclerosi Múltiple de Catalunya (Cemcat), VHIR, Hospital Universitari Vall d'Hebron, Passeig Vall d'Hebron 119-129, Barcelona 08035, Spain. Electronic address: xavier.montalban@cem-cat.org.
Xavier
X
Montalban
Universitat Autònoma de Barcelona, 08193, Bellaterra, Cerdanyola del Vallès, Spain; Servei de Neurologia-Neuroimmunologia Clínica, Centre d'Esclerosi Múltiple de Catalunya (Cemcat), VHIR, Hospital Universitari Vall d'Hebron, Passeig Vall d'Hebron 119-129, Barcelona 08035, Spain. Electronic address: carmen.espejo@vhir.org.
Carmen
C
Espejo
Gene and Cell Therapy Laboratory, Vall d'Hebron Institut de Recerca (VHIR), Passeig Vall d'Hebron 119-129, Barcelona 08035, Spain; Universitat Autònoma de Barcelona, 08193, Bellaterra, Cerdanyola del Vallès, Spain. Electronic address: jordi.barquinero@vhir.org.
Jordi
J
Barquinero
D019264:Adoptive Transfer; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001324:Autoantigens / Q000627:therapeutic use*; D001854:Bone Marrow Cells / Q000502:physiology; D002490:Central Nervous System / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D000072737:Myeloid-Derived Suppressor Cells / Q000187:drug effects / Q000502:physiology*; D012190:Retroviridae / Q000235:genetics; D012720:Severity of Illness Index; D013154:Spleen / Q000473:pathology; D050994:Voltage-Dependent Anion Channels
D001324:Autoantigens; D016207:Cytokines; D008070:Lipopolysaccharides; D050994:Voltage-Dependent Anion Channels; D007371:Interferon-gamma
Cell therapy; Experimental autoimmune encephalomyelitis; Immune tolerance; MHC class II; Multiple sclerosis; Myeloid-derived suppressor cells; PD-1; PD-L1; Regulatory B cells