Bone marrow mesenchymal stem cells inhibit the response of naive and memory antigen-specific T cells to their cognate peptide.
Mesenchymal stem cells (MSCs) have been recently shown to inhibit T-cell proliferation to polyclonal stimuli. We characterized the effect of MSCs of bone marrow origin on the T-cell response of naive and memory T cells to their cognate antigenic epitopes. The immune response to murine male transplantation antigens, HY, was selected because the peptide identity and major histocompatibility complex (MHC) restriction of the immunodominant epitopes are known. C57BL/6 female mice immunized with male cells were the source of memory T cells, whereas C6 mice transgenic for HY-specific T-cell receptor provided naive T cells. Responder cells were stimulated in vitro with male spleen cells or HY peptides in the presence or absence of MSCs. MSCs inhibited HY-specific naive and memory T cells in a dose-dependent fashion and affected cell proliferation, cytotoxicity, and the number of interferon gamma (IFN-gamma)-producing HY peptide-specific T cells. However, the MSC inhibitory effect did not selectively target antigen-reactive T cells. When MSCs were added to the T-cell cultures in a Transwell system or MSCs were replaced by MSC culture supernatant, the inhibitory activity was abrogated. T-cell reactivity was also restored if MSCs were removed from the cultures. The expression of MHC molecules and the presence in culture of antigen-presenting cells (APCs) or of CD4(+)/CD25(+) regulatory T cells were not required for MSCs to inhibit. We conclude that MSCs inhibit naive and memory T-cell responses to their cognate antigens. Overall our data suggest that MSCs physically hinder T cells from the contact with APCs in a noncognate fashion.
Krampera
Mauro
M
Department of Immunology and Transplantation Biology, Imperial College Faculty of Medicine, Hammersmith Hospital, London, United Kingdom.
Glennie
Sarah
S
Dyson
Julian
J
Scott
Diane
D
Laylor
Ruthline
R
Simpson
Elizabeth
E
Dazzi
Francesco
F
D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation; D001854:Bone Marrow Cells / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000502:physiology; D002450:Cell Communication; D002454:Cell Differentiation; D002478:Cells, Cultured / Q000276:immunology; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic; D004306:Dose-Response Relationship, Immunologic; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000276:immunology*; D005260:Female; D006183:H-2 Antigens / Q000276:immunology; D006182:H-Y Antigen / Q000737:chemistry / Q000276:immunology*; D007114:Immunization; D007156:Immunologic Memory / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D008648:Mesoderm / Q000166:cytology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008969:Molecular Sequence Data; D039902:Multipotent Stem Cells / Q000502:physiology*; D010446:Peptide Fragments / Q000276:immunology; D017154:Stromal Cells / Q000502:physiology; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D015815:Cell Adhesion Molecules; D017077:Culture Media, Conditioned; D018984:Epitopes, T-Lymphocyte; D006183:H-2 Antigens; D006182:H-Y Antigen; D010446:Peptide Fragments; D007371:Interferon-gamma