The CD8+ Leu-7+ subset of T cells in Crohn's disease: distinction between cytotoxic and covert suppressor functions.
An expanded T cell subpopulation (CD8+ Leu-7+) has previously been reported in the peripheral blood of patients with Crohn's disease. This subpopulation of T cells was associated with a 'covert suppressor' function, particularly in patients with mild/early Crohn's disease, suppressing immunoglobulin production in vitro when cultured in the presence of pokeweed mitogen. T cells with the same CD8+ Leu-7+ phenotype have also been shown to exhibit non-major histocompatability complex-restricted cytotoxicity when triggered by anti-CD3 antibodies, and this cytotoxic activity has also been shown to be elevated in patients with Crohn's disease. Because cytotoxic cells can have immunoregulatory properties, we investigated the possible relationship between the cytotoxic and 'covert suppressor' functions of the CD8+ Leu-7+ subset of T lymphocytes in patients with mildly active Crohn's disease. Although the correlation between T cell cytotoxic activity and the CD8+ Leu-7+ cells was confirmed, no evidence for covert suppressor activity was found; there were no significant differences between the amount of IgM secreted by B cells from normal subjects and patients with Crohn's disease when cultured with T cells at increasing T:B ratios. In addition, IgM production by peripheral blood B cells did not correlate with either the number of CD8+ Leu-7+ cells or with the level of cytotoxic T cell activity. Furthermore, when B cells and CD4+ T cells were co-cultured with increasing numbers of CD8+ T cells, there was no evidence for excessive suppressor T cell activity in Crohn's disease. Although some patients exhibited low levels of IgM production, this was due to diminished B cell function, rather than excessive T suppressor activity or defective T helper activity. We conclude that the CD8+ Leu-7+ T cell subset is associated with cytotoxic but not with enhanced or covert suppressor activity in Crohn's disease. The previously described covert suppressor function attributed to cells with this phenotype in Crohn's disease was not found to account for diminished B cell responsiveness in vitro and is unlikely to be of major pathophysiologic significance in the majority of patients.
Department of Medicine, University of California, Los Angeles School of Medicine.
R L
RL
Deem
S R
SR
Targan
A
A
Niederlehner
F
F
Shanahan
D000943:Antigens, Differentiation / Q000032:analysis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D001402:B-Lymphocytes / Q000276:immunology; D018959:CD57 Antigens; D016827:CD8 Antigens; D002478:Cells, Cultured; D003424:Crohn Disease / Q000276:immunology*; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D006801:Humans; D007075:Immunoglobulin M / Q000096:biosynthesis; D011043:Pokeweed Mitogens / Q000494:pharmacology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D000943:Antigens, Differentiation; D000945:Antigens, Differentiation, T-Lymphocyte; D018959:CD57 Antigens; D016827:CD8 Antigens; D007075:Immunoglobulin M; D011043:Pokeweed Mitogens