title: Distinctive pattern of cytokine production and adhesion molecule expression in peripheral blood memory CD4+ T cells from patients with active Crohn's disease.
abstract: An expansion of both circulating and intestinal lamina propria CD4+ CD45RO+ T cells has been described in patients with Crohn's disease. We studied both the cytokine profile and the expression of adhesion molecules on this T-cell subset. Peripheral blood CD4+ CD45RO+ T cells from patients with Crohn's disease (n=45) were assessed by flow cytometry and RT-PCR methods. The cytokine profile was also measured in intestinal lamina propria from seven patients. They were classified according to the CDAI and the results were compared with those of patients with ulcerative colitis (n=21) and noninflammatory intestinal conditions (n=15), and healthy controls (n=39). The mean percentage of circulating CD4+ CD45RO+ T cells producing intracellular TNF was higher in active than in inactive Crohn's disease patients (p < 0.001), active (p = 0.49) and inactive ulcerative colitis (p = 0.019), and healthy controls (p =0. 017). TNF expression correlated with CDAI (p < 0.001). An increased expression of intracellular IL-2, IL-6, and IL-10 in active Crohn's disease patients was also found. CD62L was downregulated in active Crohn's disease patients while no differences were observed in CD49d and CD11a expression. Lamina propria CD4+ CD45RO+ T cells from active Crohn's disease lesions showed an increased intracellular staining of TNF, IFN-gamma, and IL-10. Both peripheral and intestinal mucosa CD4+ CD45RO+ T cells from active Crohn's disease patients show an increased production of TNF. In addition, the circulating CD4+ CD45RO+ T-cell subset expresses a pattern of adhesion molecules that promotes homing to extranodal lymphoid tissues. This T-cell subset may play a relevant role in the immunopathogenesis of Crohn's disease.
authors.affiliation: Laboratorio de Inmunología Clínica y Oncología, Unidad asociada I+D del Consejo Superior de Investigaciones Científicas, Departamento de Medicina, Universidad de Alcalá, Alcalá de Henares, Spain.
authors.forename: Jaime
authors.initials: J
authors.lastname: García de Tena
authors.forename: Luis
authors.initials: L
authors.lastname: Manzano
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Leal
authors.forename: Esther
authors.initials: E
authors.lastname: San Antonio
authors.forename: Verónica
authors.initials: V
authors.lastname: Sualdea
authors.forename: Melchor
authors.initials: M
authors.lastname: Alvarez-Mon
mesh_terms: D000293:Adolescent; D000328:Adult; D040881:CD11a Antigen / Q000096:biosynthesis; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000096:biosynthesis*; D003424:Crohn Disease / Q000276:immunology* / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D039441:Integrin alpha4 / Q000096:biosynthesis; D019041:L-Selectin / Q000096:biosynthesis; D017493:Leukocyte Common Antigens / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D009092:Mucous Membrane / Q000276:immunology
chemical_list: D040881:CD11a Antigen; D015815:Cell Adhesion Molecules; D016207:Cytokines; D019041:L-Selectin; D039441:Integrin alpha4; D017493:Leukocyte Common Antigens