Mechanism of a lymphocyte abnormality associated with HLA-B8/DR3: role of interleukin-1.
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 mononuclear cells of five low responder individuals with HLA-B8/DR3 stimulated with 0.05 micrograms/ml of phytohaemagglutinin (PHA) accumulated only 0.036 U/ml of IL-1 compared with 0.32 U/ml for normal responders. 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 less than 0.0001) 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.
Hashimoto
S
S
Department of Medicine, Louisiana State University, School of Medicine, New Orleans.
Michalski
J P
JP
Berman
M A
MA
McCombs
C
C
D000328:Adult; D015795:HLA-B8 Antigen / Q000032:analysis*; D015803:HLA-DR3 Antigen / Q000032:analysis*; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis / Q000502:physiology*; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000276:immunology*; D008214:Lymphocytes / Q000378:metabolism; D008875:Middle Aged
D015795:HLA-B8 Antigen; D015803:HLA-DR3 Antigen; D007375:Interleukin-1; D007376:Interleukin-2