Abstract
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.
| Original language | English |
|---|---|
| Article number | N/A |
| Pages (from-to) | 3722-3729 |
| Number of pages | 8 |
| Journal | Blood |
| Volume | 101 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - 1 May 2003 |
Keywords
- Amino Acid Sequence Animals Antigen Presentation Bone Marrow Cells/*physiology Cell Adhesion Molecules/physiology Cell Communication Cell Differentiation Cells, Cultured/immunology Coculture Techniques Culture Media, Conditioned/pharmacology Cytotoxicity, Immunologic Dose-Response Relationship, Immunologic Epitopes, T-Lymphocyte/chemistry/*immunology Female H-2 Antigens/immunology H-Y Antigen/chemistry/*immunology Immunization Immunologic Memory/*immunology Interferon-gamma/biosynthesis Lymphocyte Activation/*immunology Male Mesoderm/*cytology Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, Inbred CBA Molecular Sequence Data Multipotent Stem Cells/*physiology Peptide Fragments/immunology Stromal Cells/physiology T-Lymphocyte Subsets/*immunology