T-cell immunoregulation in patients with inflammatory bowel disease. II. Enhanced suppressor T-cell activity in ulcerative colitis.
In a recent study, we have shown that peripheral blood B cells from patients with ulcerative colitis (UC) synthesized less immunoglobulin (Ig) in co-culture with autologous T cells than normal adults' B cells. When UC patients' T cells were co-cultured with normal adults' B cells, Ig synthesis was significantly decreased as compared with normal controls. In contrast, Crohn's disease (CD) patients' B and T cells functioned normally. In the present study, the activity of suppressor T cells in patients with UC and CD was determined. Peripheral blood B and T cells with monocytes were obtained from patients and normal adults of the same age and sex, and co-cultured for 10 days with pokeweed mitogen (PWM). Suppressor T-cell function was measured in mixed co-culture assays in which graded numbers of normal or patient's T cells were added to normal adults' B and T cells with PWM. Immunoglobulins (Ig) M, G and A were measured in culture supernatants using a sensitive enzyme-linked immunosorbent assay. The quantity of Ig present in the culture supernatants was determined from a standard curve. T cells from UC patients significantly decreased immunoglobulin production by control B and T cells (IgM and IgA, p = 0.02; IgG, p = 0.01). In contrast, addition of T cells from CD patients produced no significant differences. Complement mediated, monoclonal OKT8 antibody directed cell lysis revealed that the inhibition observed with UC patients' T cells in co-culture was due to a T8+ suppressor T cell. The degree of inhibition of immunoglobulin synthesis did not correlate with disease activity, duration of illness, location of disease, or corticosteroid treatment. Thus, patients with ulcerative colitis display enhanced suppressor T-cell activity in peripheral blood while patients with CD show normal helper and suppressor T-cell functions. These results provide evidence supporting a role for altered immunoregulatory activity in the pathogenesis of ulcerative colitis.
Kramer
J K
JK
Gastrointestinal Disease Research Unit, Hotel Dieu Hospital, Kingston, Ontario, Canada.
Depew
W T
WT
Szewczuk
M R
MR
D000328:Adult; D000368:Aged; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D003093:Colitis, Ulcerative / Q000276:immunology*; D003424:Crohn Disease / Q000276:immunology*; D006801:Humans; D007070:Immunoglobulin A / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D008211:Lymphocyte Cooperation; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology; D011043:Pokeweed Mitogens / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D011043:Pokeweed Mitogens