IDO expression on decidual and peripheral blood dendritic cells and monocytes/macrophages after treatment with CTLA-4 or interferon-gamma increase in normal pregnancy but decrease in spontaneous abortion.
Recent data demonstrated that CD4+CD25+ regulatory T (Treg) cells and an enzyme called indoleamine 2,3-dioxygenase (IDO) mediate maternal tolerance to the fetus. Interestingly, Treg cells express the CTLA-4 molecule on their surface, and B7 (CD80/86) ligation by CTLA-4 enhanced IDO activity of dendritic cells (DCs) and monocytes by the induction of interferon gamma (IFN-gamma) production. In this study, we studied the IDO expression on peripheral blood monocytes and decidual monocytes or DCs after treatment with CTLA-4/Fc fusion protein or IFN-gamma using flow cytometry. IDO expressions on both peripheral blood DC and decidual DC and monocytes were up-regulated during normal pregnancy. On the other hand, both IDO expression on DC and monocytes after IFN-gamma treatment or CTLA-4 treatment were decreased in spontaneous abortion cases. The expression of CD86 on peripheral blood and decidual monocytes and DC in spontaneous abortion cases was lower compared with those in normal pregnancy subjects. Also, IFN-gamma production by decidual and peripheral blood mononuclear cells after CTLA-4/Fc treatment in spontaneous abortion cases was significantly lower than those in normal pregnancy subjects. These data suggest that CTLA-4 on Treg cells up-regulates IDO expression on decidual and peripheral blood DC and monocytes by the induction of IFN-gamma production.
Miwa
Naoko
N
Department of Obstetrics and Gynecology, Toyama Medical and Pharmaceutical University, Toyama, Japan.
Hayakawa
Satoshi
S
Miyazaki
Satomi
S
Myojo
Subaru
S
Sasaki
Yasushi
Y
Sakai
Masatoshi
M
Takikawa
Osamu
O
Saito
Shigeru
S
D000022:Abortion, Spontaneous / Q000201:enzymology; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000494:pharmacology*; D060908:CTLA-4 Antigen; D003656:Decidua / Q000187:drug effects / Q000201:enzymology*; D003712:Dendrites / Q000187:drug effects / Q000201:enzymology*; D005260:Female; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000235:genetics*; D007371:Interferon-gamma / Q000502:physiology*; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology; D009000:Monocytes / Q000187:drug effects / Q000201:enzymology; D011247:Pregnancy; D012016:Reference Values
D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007371:Interferon-gamma