Unconjugated bilirubin inhibits in vitro cytotoxic T lymphocyte activity of human lymphocytes.
Septic complications have been major problems in the management of patients with obstructive jaundice and neonatal jaundice. This study investigates effects bilirubin on human T lymphocyte responses against allogeneic mixed lymphocyte reaction. In vitro exposure of human peripheral blood mononuclear cells (PBMNC) with unconjugated bilirubin at pathological levels (6 to 12 mg/dl) did not alter the subsets of CD3, CD4, CD8, CD14, CD19 and CD56 positive populations, or expression of costimulatory surface molecules CD2, CD3, CD4 and CD8. Further incubation of bilirubin-treated PBMNC with irradiated B lymphoid Raji cells after removal of the extracellular bilirubin resulted in a dose-dependent decrease of cytotoxic T lymphocyte (CTL) activity, DNA synthesis, and expression of Tac antigen (CD25) and transferrin receptor (CD71). However, no significant change of interleukin-2 (IL-2) production was observed after this incubation between bilirubin-treated and -untreated PBMNC. These results suggest that bilirubin inhibits the induction of CTL activity, and this defect may result from the impaired responsiveness against IL-2. These observations may help explain the increased infection observed in hyperbilirubinemic patients.
Haga
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Department of Internal Medicine, University of Nebraska Medical Center, Omaha 68198, USA.
Tempero
M A
MA
Zetterman
R K
RK
D000906:Antibodies / Q000276:immunology; D015703:Antigens, CD / Q000032:analysis / Q000096:biosynthesis; D000944:Antigens, Differentiation, B-Lymphocyte / Q000096:biosynthesis; D001402:B-Lymphocytes / Q000276:immunology; D001663:Bilirubin / Q000494:pharmacology*; D003602:Cytotoxicity, Immunologic; D004247:DNA / Q000378:metabolism; D004261:DNA Replication / Q000187:drug effects; D005786:Gene Expression Regulation; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis; D007565:Jaundice / Q000276:immunology; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D011990:Receptors, Transferrin; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects* / Q000276:immunology*
D000906:Antibodies; D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; C068126:CD71 antigen; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D011990:Receptors, Transferrin; D004247:DNA; D001663:Bilirubin