T-cell abnormalities in inflammatory bowel disease are mediated by interleukin 2

Inflammatory bowel disease (IBD) may be an immunologically mediated disorder in which T cells are unable to respond appropriately to cell surface-associated antigens. To test this possibility, 37 patients with IBD, 24 with Crohn's disease and 13 with ulcerative colitis who were not being treated with immunosuppressive therapy were studied. The ability of T cells to proliferate in response to autologous or allogeneic cells, i.e., the autologous or allogeneic mixed-lymphocyte reaction (MLR) was tested. The autologous MLR was depressed using patient cells compared to control cells, regardless of disease type or activity (1564 ± 223 cpm versus 3300 ± 381 cpm, P < 0.05) while the allogeneic MLR was depressed in patients with active disease only (29,833 ± 2871 cpm versus 46,799 ± 3340 cpm, P < 0.01). The ability of T cells to recognize and lyse allogeneic cells, allogeneic cell-mediated lympholysis (CML), was also low in patients with active disease (24 ± 4% versus 37 ± 3%, P < 0.05). Since T-cell proliferation and cytotoxicity depend upon adequate production of and response to a T-cell growth factor, interleukin 2 (IL-2), IL-2 production and responsiveness in IBD were studied. IL-2 production by patient T cells in response to phytohemagglutinin was only 39% of control values, P < 0.05. The response to IL-2 was measured by the increase in T-cell proliferation in the autologous MLR in medium alone or medium supplemented with IL-2. Control T-cell proliferation rose from 3300 ± 381 cpm to 10,761 ± 428 cpm with exogenous IL-2 ( P < 0.001). Patient T-cell proliferation rose from 1564 ± 223 cpm to 6817 ± 771 cpm with IL-2 ( P < 0.001) but did not reach the level of the IL-2-supplemented control autologous MLR ( P < 0.05). In addition, the percentage of activated patient T cells having Tac antigen (IL-2 receptor) was depressed ( P < 0.05). These findings did not vary with disease type or activity. It is concluded from these data that peripheral blood T lymphocytes from patients with IBD have a diminished response to cell surface antigens which is associated with a decrease in IL-2 production and receptor generation. These defects may be responsible for the depressed T-cell proliferation and cytotoxicity that accompany IBD.