Open AccessMechanism of a lymphocyte abnormality associated with HLA‐B8/DR3: role of interleukin‐1
Author(s) -
HASHIMOTO S.,
MICHALSKI J. P.,
BERMAN M. A.,
McCOMBS C.
Publication year - 1990
Publication title -
clinical & experimental immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 135
eISSN - 1365-2249
pISSN - 0009-9104
DOI - 10.1111/j.1365-2249.1990.tb05183.x
Subject(s) - phytohaemagglutinin , immunology , interleukin , lymphocyte , interleukin 2 , t lymphocyte , endocrinology , medicine , biology , cytokine , antigen
SUMMARY Lymphocytes from normal individuals with the histocompatibility antigens HLA‐B8 and DR3 have impaired proliferative responses when stimulated with suboptimal concentrations of mitogens. We have previously shown that an important factor in the impaired response is a failure to produce normal quantities of interleukin‐2 (IL‐2). To examine the mechanism of decreased responsiveness further, we measured interleukin‐1 (IL‐1) production of low responder subjects compared with controls. The peripheral blood mononuelear cells of five low responder individuals with HLA‐B8/ DR3 stimulated with 0.05 μg/ml of phytohaemagglutinin (PHA) accumulated only 0.036 U/ml of IL‐I compared with 0.32 U/ml for normal respondcrs. There was a highly significant correlation between the PHA‐stimulated IL‐1 concentration at 12 h and the subsequent IL‐2 concentration at 48 h ( r =0.89, P <0.000l) suggesting a role of decreased IL‐1 production in the impaired response. A study of unfractionated or column‐fractionated culture supernatants revealed no evidence that the decreased IL‐1 activity in the supernatants of low responder subjects was related to increased IL‐1 inhibitor concentrations. These results suggest that impaired IL‐2 production and lymphocyte proliferation in healthy subjects with HLA‐B8/DR3 may be mediated at least in part by decreased IL‐1 production, and implicates a defect of a very early event in lymphocyte activation.