The expression and function of costimulatory molecules B7H and B7-H1 on colonic epithelial cells.
OBJECTIVE
Previous studies have suggested that intestinal epithelial cells (IECs) may function as antigen-presenting cells for CD4+ and CD8+ T cells. However, these cells fail to express conventional costimulatory molecules (CD80, CD86), leading to the possibility that antigen presented by normal IECs could result in anergy. Other members of the B7 family have recently been identified. B7h interacts with inducible costimulator (ICOS) on T cells and provides a positive signal, whereas B7-H1 and B7-DC interact with PD-1 and transmit an inhibitory signal. Our aim was to determine whether IECs express novel B7 family members and whether these molecules play a role in IEC:T-cell interactions.


METHODS
B7h and B7-H1 expression was assessed in isolated IECs and IEC lines. The functional role of B7h and B7-H1 in the interaction between IECs and T cells was assessed in coculture experiments using purified anti-B7h or B7-H1 monoclonal antibodies (mAbs), B7h immunoglobulin (Ig), or B7-H1 fusion proteins.


RESULTS
B7h and B7-H1 messenger RNA was detected in IEC lines and IECs from healthy controls and patients with inflammatory bowel disease (IBD). IECs from patients with IBD but not healthy controls expressed B7h and B7-H1 protein on their surface. Proliferation of IEC-stimulated T cells was inhibited only by B7h immunoglobulin treatment, whereas interferon gamma secretion in these cocultures was inhibited by both anti-B7h mAb and B7h Ig. No difference was seen between IBD or normal IEC populations.


CONCLUSIONS
These data suggest that the B7h-ICOS costimulatory pathway may be important in IEC:T-cell interactions.
Nakazawa
Atsushi
A
Immunobiology Center, Mount Sinai School of Medicine, 1425 Madison Avenue, New York, NY 10029, USA.
Dotan
Iris
I
Brimnes
Jens
J
Allez
Matthieu
M
Shao
Ling
L
Tsushima
Fumihiko
F
Azuma
Miyuki
M
Mayer
Lloyd
L
D015703:Antigens, CD; D018122:B7-1 Antigen; D060890:B7-H1 Antigen; D001798:Blood Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D002455:Cell Division; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D003106:Colon / Q000378:metabolism*; D006801:Humans; D060945:Inducible T-Cell Co-Stimulator Ligand; D007371:Interferon-gamma / Q000378:metabolism; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism*; D008562:Membrane Glycoproteins; D010455:Peptides / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D011506:Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D013601:T-Lymphocytes / Q000166:cytology
D015703:Antigens, CD; D018122:B7-1 Antigen; D060890:B7-H1 Antigen; D001798:Blood Proteins; C423236:CD274 protein, human; C498514:ICOSLG protein, human; D060945:Inducible T-Cell Co-Stimulator Ligand; D008562:Membrane Glycoproteins; D010455:Peptides; D011506:Proteins; D007371:Interferon-gamma