Stromal cells' B7-1 is a key stimulatory molecule for interleukin-10 production by HOZOT, a multifunctional regulatory T-cell line.
We have previously shown that xenogeneic stromal cell stimulation of naïve T cells resulted in the generation of a new type of regulatory T (Treg) cell termed HOZOT, which has multifunctional properties and a CD4/CD8 double-positive phenotype. Even after the establishment of HOZOT, stromal cells can function as an antigen-presenting cell (APC) by inducing these cells to produce interleukin (IL)-10. When compared with other stimuli, stromal cells showed an IL-10-producing ability comparable to anti-CD3 antibody (Ab) stimulation, and much greater than dendritic cell (DC) stimulation. Distinct from professional APCs, stromal cells express only major histocompatibility complex (MHC) class I and B7-1 costimulatory molecules, and not MHC class II or other costimulatory molecules, such as ICOSL (CD275), PD-L1 (CD274), PD-L2 (CD273), CD40, OX40L (CD252) and 4-1BBL (CD137L) in the absence of stimulation. Blocking experiments revealed that, in addition to anti-H-2K(d) Ab and anti-human CD8 Ab, anti-mouse B7-1 Ab could effectively block IL-10 production, indicating a key role of the B7-1/CD28 pathway. Using stromal cells expressing different levels of B7-1, IL-10 production correlated with the levels of B7-1 expression. Distinct from ICOSL or PD-L1 expressed on DCs (which are regarded as IL-10-inducing costimulatory molecules), this study showed that B7-1 on stromal cells is a key molecule regulating IL-10 production by multifunctional Treg cells, HOZOT.
Otani
Takeshi
T
Cell Biology Institute, Research Center, Hayashibara Biochemical Laboratories Inc., Fujisaki, Naka-ku, Okayama, Japan. otani@hayashibara.co.jp
Tsuji-Takayama
Kazue
K
Okochi
Ayumi
A
Yamamoto
Mayuko
M
Takeuchi
Makoto
M
Yamasaki
Fumiyuki
F
Nakamura
Shuji
S
Kibata
Masayoshi
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis; D018122:B7-1 Antigen / Q000276:immunology*; D016827:CD8 Antigens / Q000378:metabolism; D002460:Cell Line; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis*; D051379:Mice; D010641:Phenotype; D017154:Stromal Cells / Q000166:cytology / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000166:cytology* / Q000276:immunology*
D000911:Antibodies, Monoclonal; D018122:B7-1 Antigen; D016827:CD8 Antigens; D015395:Histocompatibility Antigens Class I; D016753:Interleukin-10