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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 annexing 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+CD28null 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 T-cell subset might express more intracytoplasmic TNF and IFN-γ 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+ CD28null 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+CD28null T cells expressing effector-associated cell surface molecules and displaying enhanced resistance to apoptosis. [ABSTRACT FROM AUTHOR]

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.

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.