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Defective immunoregulation in primary biliary cirrhosis: CD4+, Leu–8+ T cells have abnormal activation and suppressor function in vitro
Author(s) -
Suou Takeaki,
Civeira Maria P.,
Kanof Marjorie E.,
MorenoOtero Ricardo,
Jones E. Anthony,
James Stephen P.
Publication year - 1989
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.1840100403
Subject(s) - primary biliary cirrhosis , in vitro , suppressor , biliary cirrhosis , medicine , gastroenterology , pathology , immunology , biology , biochemistry , disease , cancer , autoimmune disease
To determine whether abnormalities of lymphocyte function in primary biliary cirrhosis are due to altered function of immunoregulatory T cell subpopulations, phenotypic and functional characteristics of CD4+ T cells were examined. The proportion of CD4+ T cells expressing the Leu‐8 and CD45R antigens was normal in patients with primary biliary cirrhosis. The capacity of CD4+, Leu‐8‐T cells to provide helper function for pokeweed mitogen‐stimulated immunoglobulin synthesis by B cells in vitro was similar in patients and controls. However, in contrast to normal individuals and patients with other liver diseases, CD4+, Leu‐8+ T cells from six of 10 patients with primary biliary cirrhosis did not suppress, but enhanced immunoglobulin synthesis. Whereas treatment of CD4+ T cells from normal individuals with anti‐Leu‐8 monoclonal antibody enhanced their suppressor function, similar treatment of CD4+ T cells from patients with primary biliary cirrhosis did not increase their suppressor function. To determine whether the abnormal regulatory function of CD4+, Leu‐8+ T cells was due to a defect of cell activation, the proliferative response of CD4+ T cell subpopulations to mitogenic stimulation was examined. The proliferative responses of CD4+, Leu‐8‐T cells from patients with primary biliary cirrhosis and controls were similar, but the proliferative responses of CD4+, Leu‐8+ T cells from patients with primary biliary cirrhosis were lower than those of control cells. Since the CD4+, Leu‐8+ T cell population plays a role in suppressing immunoglobulin synthesis and is contained within the autoreactive T cell population, the abnormal function of this T cell subpopulation in some patients with primary biliary cirrhosis may play a role in defective immunoregulation found in this disease.