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Discrete Toll‐like receptor agonists have differential effects on alloimmunization to transfused red blood cells
Author(s) -
Hendrickson Jeanne E.,
Roback John D.,
Hillyer Christopher D.,
Easley Kirk A.,
Zimring James C.
Publication year - 2008
Publication title -
transfusion
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.045
H-Index - 132
eISSN - 1537-2995
pISSN - 0041-1132
DOI - 10.1111/j.1537-2995.2008.01801.x
Subject(s) - immunology , lipopolysaccharide , flow cytometry , antigen , receptor , antibody , red blood cell , microbiology and biotechnology , biology , medicine , chemistry
BACKGROUND: Factors influencing alloimmunization to transfused red blood cells (RBCs) are not well understood. Utilizing a murine model, we have recently reported that RBC alloimmunization is enhanced by recipient treatment with viral‐like polyinosinic polycytidylic acid (poly(I:C)). To determine whether a different subtype of inflammation also enhances RBC alloimmunization, we investigated the effects of the bacterial endotoxin lipopolysaccharide (LPS) on alloimmunization. STUDY DESIGN AND METHODS: Mice were treated with poly(I:C) or LPS; in select experiments, the precursor frequency of naïve antigen‐specific CD4+ T cells was increased using T cells from T‐cell receptor transgenic mice. Recipients were transfused with leukoreduced RBCs expressing the membrane‐bound hen egg lysozyme (mHEL) antigen, and alloimmunization was measured by anti‐HEL immunoglobulin G responses using enzyme‐linked immunosorbent assay and flow cytometric cross‐match. Costimulatory molecule expression was examined on antigen‐presenting cells (APCs) by flow cytometry. RESULTS: Increased expression of costimulatory molecules on APCs was seen after treatment with either poly(I:C) and LPS. In contrast to the enhancement of RBC alloimmunization observed after treatment with poly(I:C), LPS not only failed to enhance but also actively suppressed alloimmunization, even in the presence of increased mHEL‐specific CD4+ T cells (p < 0.001 LPS vs. control). CONCLUSIONS: These data demonstrate that the regulation of RBC alloimmunization by inflammatory stimuli is complex, including enhancement by a viral‐like stimulus and suppression by a bacterial‐type stimulus. The mechanism(s) are unlikely to involve variation in the costimulatory molecules studied, because only subtle differences on APCs were observed after treatment with poly(I:C) and LPS.