We analyzed the phenotype, proliferative responsiveness, cytokine production and apoptosis susceptibility of lamina propria lymphocytes to different activation pathways. Lamina propria lymphocytes is a population enriched of activated lymphocytes showing a "memory" phenotype. As opposite to peripheral blood lymphocytes, lamina propria lymphocytes show proliferative hyporesponsiveness when stimulated via TCR/CD3 pathway while proliferative response to the CD2 activation pathway is relatively preserved. Under the latter activation pathway, cytokine production, especially IL-4 and IFN-gamma, is higher than that observed in peripheral lymphocytes. When compared to controls, lamina propria lymphocytes isolated from inflammatory bowel disease (Crohn's disease and ulcerative colitis) show distinctive variation in the cytokine production. In particular, Crohn's disease is characterized by an increased production of IFN-gamma, while in ulcerative colitis an increased production of IL-5 is observable. Among the different regulatory mechanisms contributing to maintain immunological homeostasis we analyzed the susceptibility to apoptosis of lamina propria lymphocytes. We found that CD2-activation pathway is regulated by Fas-mediated apoptosis, which regulates proliferation and cytokine production. In inflammatory bowel disease this apoptosis is defective thus contributing to the chronic inflammation and cytokine dysregulation.