Major histocompatibility complex class II-dependent antigen presentation by human intestinal endothelial cells.
OBJECTIVE
In the normal gut, human intestinal microvascular endothelial cells (HIMECs) express major histocompatibility complex (MHC) class II molecules. Enhanced expression is found in chronic inflammation. We examined the cytokine regulation of MHC class II molecules and the associated invariant chain (Ii) in HIMECs and investigated whether such cells can process and present a complex protein antigen to T cells.


METHODS
Enzyme-linked immunosorbent assay, flow cytometry, immunoelectron microscopy, as well as T-cell activation assay with HIMECs and HLA-DR-restricted T-cell clones were employed.


RESULTS
In unstimulated HIMEC monolayers, HLA-DR, -DP, and -DQ and Ii were undetectable at the protein level, but interferon gamma (IFN-gamma) (100 U/mL) induced expression that peaked for DR after 2-3 days, for DP after 4-6 days, for DQ after 10-12 days, and for Ii after 2-3 days. Tumor necrosis factor alpha had no effect alone but enhanced class II expression in combination with IFN-gamma, most notably for DQ and DP. HLA-DR3-restricted and Mycobacterium tuberculosis heat shock 65-kilodalton-specific T-cell clones were activated to produce IFN-gamma in response to relevant antigen presented by IFN-gamma-treated HIMECs. This response was inhibited by blocking monoclonal antibody to HLA-DR and by chloroquine when compared to professional antigen-presenting cells, HIMECs activated T-cell clones quite efficiently.


CONCLUSIONS
These data suggest that microvascular endothelial cells can present complex protein antigens in the human gut.
Haraldsen
G
G
Laboratory for Immunohistochemistry and Immunopathology (LIIPAT), Institute of Pathology, University of Oslo, Rikhospitalet, Oslo, Norway. guttormh@cmgm.stanford.edu
Sollid
L M
LM
Bakke
O
O
Farstad
I N
IN
Kvale
D
D
Molberg
Norstein
J
J
Stang
E
E
Brandtzaeg
P
P
D017951:Antigen Presentation; D000944:Antigens, Differentiation, B-Lymphocyte / Q000032:analysis / Q000502:physiology; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000032:analysis / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000494:pharmacology; D007422:Intestines / Q000276:immunology*; D008833:Microcirculation / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000944:Antigens, Differentiation, B-Lymphocyte; D000949:Histocompatibility Antigens Class II; D014409:Tumor Necrosis Factor-alpha; C045084:invariant chain; D007371:Interferon-gamma