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Prepublished online as a Blood First Edition Paper on December 27, 2002; DOI 10.1182/blood-2002-07-2104.
Previous Article | Table of Contents | Next Article 
Blood, 1 May 2003, Vol. 101, No. 9, pp. 3722-3729
TRANSPLANTATION
Bone marrow mesenchymal stem cells inhibit the response of naive
and memory antigen-specific T cells to their cognate
peptide
Mauro Krampera,
Sarah Glennie,
Julian Dyson,
Diane Scott,
Ruthline Laylor,
Elizabeth Simpson, and
Francesco Dazzi
From the Department of Immunology and Transplantation
Biology, Imperial College Faculty of Medicine, Hammersmith Hospital,
London, United Kingdom.
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 (IFN- )-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.

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