title: Inhibition of B-cell proliferation and antibody production by mesenchymal stromal cells is mediated by T cells.
abstract: Bone marrow (BM)-derived mesenchymal stromal cells (MSCs), endowed with immunosuppressive and anti-inflammatory properties, represent a promising tool in immunoregulatory and regenerative cell therapy. Clarifying the interactions between MSCs and B-lymphocytes may be crucial for designing innovative MSC-based strategies in conditions in which B cells play a role, including systemic lupus erythematosus (SLE) and rejection of kidney transplantation. In this study, we show that, both in healthy subjects and in patients, in vitro B-cell proliferation, plasma-cell differentiation, and antibody production are inhibited by BM-derived MSCs when peripheral blood lymphocytes are stimulated with CpG, but not when sorted B cells are cultured with MSCs+CpG. Inhibition is restored in CpG+MSC cocultures when sorted T cells are added to sorted B cells, suggesting that this effect is mediated by T cells, with both CD4(+) and CD8(+) cells playing a role. Moreover, cell-cell contact between MSCs and T cells, but not between MSCs and B cells, is necessary to inhibit B-cell proliferation. Thus, the presence of functional T cells, as well as cell-cell contact between MSCs and T cells, are crucial for B-cell inhibition. This information can be relevant for implementing MSC-based therapeutic immune modulation in patients in whom T-cell function is impaired.
authors.affiliation: 1 Immunology Research Area, Ospedale Pediatrico Bambino Gesù, IRCSS , Roma, Italy .
authors.forename: Maria Manuela
authors.initials: MM
authors.lastname: Rosado
authors.forename: Maria Ester
authors.initials: ME
authors.lastname: Bernardo
authors.forename: Marco
authors.initials: M
authors.lastname: Scarsella
authors.forename: Antonella
authors.initials: A
authors.lastname: Conforti
authors.forename: Ezio
authors.initials: E
authors.lastname: Giorda
authors.forename: Simone
authors.initials: S
authors.lastname: Biagini
authors.forename: Simona
authors.initials: S
authors.lastname: Cascioli
authors.forename: Francesca
authors.initials: F
authors.lastname: Rossi
authors.forename: Isabella
authors.initials: I
authors.lastname: Guzzo
authors.forename: Marina
authors.initials: M
authors.lastname: Vivarelli
authors.forename: Luca
authors.initials: L
authors.lastname: Dello Strologo
authors.forename: Francesco
authors.initials: F
authors.lastname: Emma
authors.forename: Franco
authors.initials: F
authors.lastname: Locatelli
authors.forename: Rita
authors.initials: R
authors.lastname: Carsetti
mesh_terms: D000293:Adolescent; D000328:Adult; D000917:Antibody Formation / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002450:Cell Communication / Q000276:immunology*; D049109:Cell Proliferation; D002648:Child; D002675:Child, Preschool; D018920:Coculture Techniques; D005260:Female; D006084:Graft Rejection / Q000276:immunology; D006801:Humans; D016030:Kidney Transplantation; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D008297:Male; D059630:Mesenchymal Stem Cells / Q000276:immunology*