Expression of CD40 and its ligand, CD40L, in intestinal lesions of Crohn's disease.
OBJECTIVE
Selected mechanisms of the immune system participate in the development of inflammatory bowel disease. Recently, overexpression of the ligand for CD40 (CD40L), a lymphocyte costimulatory molecule, was shown to induce severe inflammatory bowel disease in transgenic mice. In the present study, we examined the expression of CD40 and CD40L on surgical specimens of ileum from 12 patients with Crohn's disease and 10 patients with diverticulitis.


METHODS
Several CD40L+ cells were present in the affected tissue of patients with Crohn's disease, whereas few scattered CD40L+ cells were detected in sections of histologically normal ileum, resected distantly from the affected tissue, in patients with diverticulitis and in normal ileum portions obtained from colorectal cancer undergoing extensive surgery. The phenotype of CD40L+ cells was mainly CD4+.


RESULTS
In patients with Crohn's disease, several CD40+ cells were detectable in the same areas of lymphocytes expressing CD40L, whereas in patients with diverticulitis, the number of CD40+ cells was significantly lower. Most of the CD40+ cells costained with CD20, thus showing to be B-lymphocytes, and only a few were CD14+ macrophages. Several von Willebrand-positive vessels were also positive for CD40. In addition, several infiltrating macrophages were found to express B7-1 and B7-2 molecules, the ligands of CD28 and CTLA-4, which cooperate with the CD40-CD40L pathway in lymphocyte activation. Staining of ileal lesions with anti-CTLA-4 antibodies resulted in detection of none or very few positive cells. In contrast, in patients with diverticulitis, an enhanced number of B7-1 and B7-2 and CTLA-4 was observed.


CONCLUSIONS
The local accumulation of CD40L+ together with CD40+ cells within intestinal lesions of Crohn's disease suggests the involvement of this co-stimulatory pathway.
Battaglia
E
E
Cattedra di Nefrologia, Dipartimento di Medicina Interna, Università di Torino, Italy.
Biancone
L
L
Resegotti
A
A
Emanuelli
G
G
Fronda
G R
GR
Camussi
G
G
D000069594:Abatacept; D000328:Adult; D015703:Antigens, CD / Q000032:analysis / Q000235:genetics; D018951:Antigens, CD20 / Q000032:analysis; D000943:Antigens, Differentiation / Q000032:analysis / Q000235:genetics; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis / Q000235:genetics*; D001402:B-Lymphocytes / Q000276:immunology; D018122:B7-1 Antigen / Q000032:analysis / Q000235:genetics; D051940:B7-2 Antigen; D018106:CD28 Antigens / Q000032:analysis / Q000235:genetics; D015704:CD4 Antigens / Q000235:genetics; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D019013:CD40 Antigens / Q000032:analysis / Q000235:genetics*; D023201:CD40 Ligand; D060908:CTLA-4 Antigen; D003424:Crohn Disease / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D004239:Diverticulitis, Colonic / Q000235:genetics / Q000276:immunology / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007077:Ileal Diseases / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D007082:Ileum / Q000276:immunology / Q000378:metabolism; D018796:Immunoconjugates; D007141:Immunoglobulin Fc Fragments / Q000032:analysis / Q000235:genetics; D008024:Ligands; D018950:Lipopolysaccharide Receptors / Q000032:analysis; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis / Q000235:genetics*; D010641:Phenotype; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000235:genetics*; D014841:von Willebrand Factor / Q000032:analysis / Q000235:genetics
D015703:Antigens, CD; D018951:Antigens, CD20; D000943:Antigens, Differentiation; D000945:Antigens, Differentiation, T-Lymphocyte; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D018106:CD28 Antigens; D015704:CD4 Antigens; D019013:CD40 Antigens; C497964:CD86 protein, human; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C556707:Ctla4 protein, mouse; D018796:Immunoconjugates; D007141:Immunoglobulin Fc Fragments; D008024:Ligands; D018950:Lipopolysaccharide Receptors; D008562:Membrane Glycoproteins; D014409:Tumor Necrosis Factor-alpha; D014841:von Willebrand Factor; D023201:CD40 Ligand; D000069594:Abatacept