Active Crohn's Disease Patients Show a Distinctive Expansion of Circulating Memory CD4+CD45RO+CD28null T Cells.

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⁺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 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⁺ 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. [ABSTRACT FROM AUTHOR]