title: Active Crohn's disease patients show a distinctive expansion of circulating memory CD4+CD45RO+CD28null T cells.
abstract: In a previous study we found an expansion of circulating memory (CD45RO(+)) CD4(+) T cells in patients with Crohn's disease (CD). The aim of this work was to investigate the phenotypic and functional characteristics of this T-cell subset in CD. We analyzed in peripheral blood CD4(+)CD45RO(+) T cells from CD patients the expression of surface markers associated to immune activation, costimulation, and apoptosis. In sorted CD4(+)CD45RO(+) T cells apoptosis was quantified by fluorescent annexin V binding. Healthy subjects and patients with ulcerative colitis and acute bacterial enterocolitis served as control groups. An increased percentage of memory CD4(+)CD45RO(+) T cells lacking the expression of costimulatory receptor CD28 was detected in patients with active CD when compared to the other groups evaluated. This expanded CD4(+)CD45RO(+)CD28(null) T-cell subset expressed mostly the effector-cell marker CD57(+). Both CD28 downregulation and CD57 expression correlated to CDAI and surrogate markers of disease activity. These phenotypic changes observed on CD4(+)CD45RO(+) T cells from active CD returned to values similar to healthy controls after clinical remission. Moreover, this memory CD28(null) T-cell subset might express more intracytoplasmic TNF and IFN-gamma than their CD28(+) counterpart. Significantly lower frequencies of memory CD4(+)CD45RO(+) T cells expressing CD95 apoptosis receptor were found in patients with active CD. Moreover, sorted CD4(+)CD45RO(+)and CD4(+)CD45RO(+) CD28(null) T cells from patients with active CD exhibited a lower apoptotic rate than that found in healthy controls and inactive CD patients. According to our data, circulating T lymphocytes from active CD patients show distinctive phenotypic and functional changes, characterized by an expansion of memory CD4(+)CD45RO(+)CD28(null) T cells expressing effector-associated cell surface molecules and displaying enhanced resistance to apoptosis.
authors.affiliation: Laboratorio de Inmunología Clínica y Oncología, Unidad asociada I+D del Consejo Superior de Investigaciones Científicas, Departamento de Medicina, Universidad de Alcalá, Alcala 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: D000328:Adult; D017209:Apoptosis; D018106:CD28 Antigens / Q000032:analysis / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003424:Crohn Disease / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D006801:Humans; D007156:Immunologic Memory; D017493:Leukocyte Common Antigens / Q000032:analysis / Q000276:immunology*; D008297:Male
chemical_list: D018106:CD28 Antigens; D016207:Cytokines; D017493:Leukocyte Common Antigens