Impaired mitogenic response of peripheral blood T cells in ulcerative colitis is not due to apoptosis.

Abstract

An abnormal immune response may play a pathogenic role in ulcerative colitis (UC). Animal models suggest that T-cell regulation may be of central importance in the inflammatory process. Our aims were the characterization of the phenotype and functional status of circulating T-cells in ulcerative colitis patients and to determine if activation-induced cell death in CD4 and CD8 lymphocytes in patients differs from healthy controls. Forty-eight patients (24 women and 24 men) fulfilling the histopathological, clinical, and immunological criteria for UC were studied. T-cell phenotype and function were studied in blood lymphocytes from patients with ulcerative colitis and healthy donors by flow cytometric analysis, as well as [3H]thymidine incorporation. There were no significant differences in the percentage of T-cell subpopulations (CD3, CD4, CD8) and NK cells in the different groups. The percentage of cells in growth phase S+G2M at two and three days of phytohemagglutinin (PHA) stimulation was significantly decreased in UC patients, but the percentage of CD4+ and CD8+ cells in UC patients that showed apoptosis was not significantly different than that in the control group. Proliferative responses to IL-4 also suggested that a reduced responsiveness to this cytokine may be involved in UC. In conclusion, the impaired proliferative response to PHA of T lymphocytes from UC patients is not associated with an in vitro increase in the apoptotic response in CD4+ or CD8+ cells. A reduced IL-4 response may be involved in this peculiar mitogenic response. These changes may be pathogenic or a favorable adaptive mechanism.