T-cell immunoregulation in patients with inflammatory bowel disease. I. Differential helper T-cell function in ulcerative colitis and Crohn's disease

The role of helper T-cells in patients with ulcerative colitis (UC) and Crohn's disease (CD) was investigated. Peripheral blood B- and T-cells with or without monocytes were obtained from patients and normal adults of the same age and sex, and co-cultured for 10 days with pokeweed mitogen (PWM). Immunoglobulins (Ig) M, G and A were measured in the culture supernatants using a sensitive enzyme-linked immunosorbent assay. The quantity of Ig present in the culture supernatants was determined from a standard curve. Immunoglobulins M, G and A synthesis and secretion by B-cells in the presence of T-cells required monocytes and PWM. The data indicate that co-cultures of heterologous normal adult T-cells and B-cells with PWM did not significantly affect Ig synthesis as compared with autologous cultures. Autologous cultures of CD patients' B- and T-cells were found not to be significantly different from normals in their capacity to synthesize Ig. In contrast, autologous UC patients' B- and T-cells were found to be significantly less effective as compared with normal adults' co-cultures in the synthesis Ig. When CD patients' T-cells were in co-culture with normal adults' B-cells, Ig synthesis was maintained. However, a marked diminution in Ig synthesis was seen when UC patients' T-cells were used in co-culture with normal adults' B-cells. The degree of inhibition of immunoglobulin synthesis did not correlate with disease activity, duration of illness, location of disease, or corticosteroid treatment. These results suggest that patients with ulcerative colitis have an altered helper T-cell population while CD patients' T-cells are either normal or hyperactive in the capacity to provide helper function in PWM-induced immunoglobulin secretion by peripheral blood B-cells.