T cell-B cell regulation in the intestinal lamina propria in Crohn's disease

Many patients with Crohn's disease have suppressor T cells circulating in the peripheral blood that are potent inhibitors of immunoglobulin synthesis in vitro. The purpose of this study was to examine the regulatory effects of T cells isolated from the lamina propria of patients with Crohn's disease or of patients with other diseases. Lamina propria cells were isolated from surgically resected intestine by sequential ethylenediaminetetraacetic acid and collagenase incubations. T cells were purified from lamina propria either by anti-F(ab)2' affinity columns or by a panning technique using monoclonal anti-T cell antibodies. Changes in the pokeweed mitogen-stimulated synthesis of immunoglobulin M, immunoglobulin G, and immunoglobulin A by normal peripheral blood indicator lymphocytes, as measured by sandwich enzyme-linked immunosorbent assay, was used as an index of help and suppression. Helper T-cell activity was sought by coculturing lamina propria T cells with normal peripheral blood cells plus pokeweed mitogen. Helper T-cell activity was found among lamina propria T-cell populations of patients and controls to a roughly comparable extent; help was provided for all isotypes. Suppressor T-cell activity was sought by coculturing lamina propria T-cells with normal B cells plus irradiated normal T cells plus pokeweed mitogen. No significant suppressor T-cell activity was observed in these cocultures, whether the cells were obtained from control intestine, the grossly uninvolved margin of Crohn's disease intestine, or actively inflamed Crohn's disease intestine. We conclude that suppressor T-cell activity of the sort found previously in the peripheral blood of patients with Crohn's disease is not demonstrable in the intestinal lesions of Crohn's disease. Helper T-cell activity is the predominant regulatory activity in both control and inflamed intestinal lamina propria.