An increased number of CD40-high monocytes in patients with Crohn's disease.
OBJECTIVE
CD40-CD40 ligand (CD40L) interaction is essential for the T-lymphocyte-dependent immune response. This interaction may be operational in the pathogenesis of inflammatory bowel diseases (IBD). The present study examined the expression of CD40 in peripheral blood mononuclear cells (PBMNCs) and tissue specimens, and CD40-stimulated interleukin (IL)-12 release from PBMNCs in IBD.


METHODS
The expression of CD40 in PBMNCs and tissue inflammatory cells was examined by flowcytometry and immunohistochemistry, respectively. IL-12 release was measured in cultured media of PBMNCs by an enzyme-linked immunosorbent assay.


RESULTS
Most peripheral blood B-lymphocytes expressed CD40 in all subjects. However, in ulcerative colitis (UC) patients, a significantly increased mean fluorescence intensity (MFI) of CD40 on B-lymphocytes was detected, compared with control subjects and patients with Crohn's disease (CD). In contrast, both the percentage positivity and MFI of CD40 on monocytes of active CD subjects were significantly increased, compared with the other groups. In active CD patients, a high level of IL-12 release from PBMNCs was observed by CD40 stimulation, compared with those of the other groups. When primed with IFN-gamma, PBMNCs from inactive CD patients released a significantly high level of IL-12, probably via stimulation by the CD40 monoclonal antibody. In the affected mucosa of CD, numerous CD40-positive cells were demonstrated, and they were also CD68-positive, suggesting these double CD40/ CD68-positive cells are tissue macrophages.


CONCLUSIONS
These results suggest that the examination of CD40 expression in PBMNCs might enable the differentiation of CD from UC. CD40-high monocytes in CD patients may play a role in the pathogenesis of CD.
Sawada-Hase
N
N
Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, Japan.
Kiyohara
T
T
Miyagawa
J
J
Ueyama
H
H
Nishibayashi
H
H
Murayama
Y
Y
Kashihara
T
T
Nakahara
M
M
Miyazaki
Y
Y
Kanayama
S
S
Nezu
R
R
Shinomura
Y
Y
Matsuzawa
Y
Y
D000293:Adolescent; D000328:Adult; D019013:CD40 Antigens / Q000032:analysis*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002452:Cell Count; D002478:Cells, Cultured; D003093:Colitis, Ulcerative / Q000276:immunology / Q000473:pathology; D003424:Crohn Disease / Q000276:immunology* / Q000473:pathology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D018664:Interleukin-12 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology* / Q000473:pathology*; D013194:Staining and Labeling
D019013:CD40 Antigens; D015815:Cell Adhesion Molecules; D018664:Interleukin-12