Ca2+ signaling in identified T-lymphocytes from human intestinal mucosa. Relation to hyporeactivity, proliferation, and inflammatory bowel disease

Abstract

Ca2+ entry across the plasma membrane is necessary for the activation and proliferation of T-lymphocytes. Human intestinal lamina propria lymphocytes physiologically exhibit minimal proliferation in response to antigen receptor stimulation when compared with peripheral blood T-lymphocytes. This hyporeactivity is partially abolished in inflammatory bowel disease. We hypothesized that differences in Ca2+ signaling could be related to the disease. To test this possibility, we measured Ca2+ signals in identified lymphocytes from human blood and human intestinal mucosa. Ca2+ signals in lamina propria T-lymphocytes from non-inflamed tissue were drastically reduced when compared with Ca2+ signals of blood T-lymphocytes from the same persons. However, Ca2+ signals in T-lymphocytes from inflamed intestinal mucosa were much higher than the ones from non-inflamed mucosa and almost reached levels of Ca2+ signals in peripheral blood T-cells. Furthermore, Ca2+ influx was closely linked to cell proliferation in both peripheral blood T-lymphocytes and lamina propria lymphocytes cells. We conclude that differences in Ca2+ signaling can explain the differences of T-lymphocyte reactivity in blood versus lamina propria and, importantly, also between T-lymphocytes from inflamed and non-inflamed intestinal mucosa. Ca2+ channels in the plasma membrane of T-lymphocytes might thus prove an excellent target to screen for immunosuppressiva to potentially treat the symptoms of inflammatory bowel disease.