title: Mechanisms of the immunosuppressive effects of mouse adipose tissue-derived mesenchymal stromal cells on mouse alloreactively stimulated spleen cells.
abstract: The mechanisms of immunomodulation by mesenchymal stromal cells remain poorly understood. In this study, the effects of mouse adipose tissue-derived mesenchymal stromal cells (ASCs) on mouse spleen cells alloreactively stimulated by anti-CD3 and anti-CD28 antibody-coated (anti-CD3/CD28) beads were observed. Production of interferon-γ by the anti-CD3/CD28 bead-stimulated spleen cells was significantly suppressed in co-culture with ASCs. However, an augmented intensity of CD69 on the stimulated spleen cells was not suppressed in the presence of ASCs. The immunosuppressive effects of ASCs were partially mediated by one or more soluble factors (26% suppression). However, the ASCs require cell-cell contact in order to maximally exert suppression (88%). The suppressive effect of ASCs mediated by direct cell contact was partially reversed following knockdown of β2 microglobulin, a component of the major histocompatibility complex (MHC) class I molecule, with siRNA. The results of the study demonstrated that ASCs have significant immune modulatory effects on alloreactively stimulated spleen cells. The effects of ASCs on spleen cells are dependent on soluble factor(s) and cell contact, which is mediated by the MHC class I complex on ASCs.
authors.affiliation: Department of Oral Implantology, Asahi University School of Dentistry, Mizuho-shi, Gifu 501-0296, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Nagaya
authors.affiliation: Department of Oral Biochemistry, Asahi University School of Dentistry, Mizuho-shi, Gifu 501-0296, Japan.
authors.forename: Masako
authors.initials: M
authors.lastname: Mizuno-Kamiya
authors.affiliation: Department of Oral Biochemistry, Asahi University School of Dentistry, Mizuho-shi, Gifu 501-0296, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Takayama
authors.affiliation: Department of Oral Biochemistry, Asahi University School of Dentistry, Mizuho-shi, Gifu 501-0296, Japan.
authors.forename: Harumi
authors.initials: H
authors.lastname: Kawaki
authors.affiliation: Department of Oral Implantology, Asahi University School of Dentistry, Mizuho-shi, Gifu 501-0296, Japan.
authors.forename: Ippei
authors.initials: I
authors.lastname: Onoe
authors.affiliation: Department of Oral Implantology, Asahi University School of Dentistry, Mizuho-shi, Gifu 501-0296, Japan.
authors.forename: Toshiichiro
authors.initials: T
authors.lastname: Tanabe
authors.affiliation: Department of Oral Implantology, Asahi University School of Dentistry, Mizuho-shi, Gifu 501-0296, Japan.
authors.forename: Kuniteru
authors.initials: K
authors.lastname: Nagahara
authors.affiliation: Department of Oral Biochemistry, Asahi University School of Dentistry, Mizuho-shi, Gifu 501-0296, Japan.
authors.forename: Nobuo
authors.initials: N
authors.lastname: Kondoh
keywords: adipose tissue-derived stromal cells; immunosuppression; interferon-γ; β2 microglobulin