Discrete Toll-like receptor agonists have differential effects on alloimmunization to transfused red blood cells.
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.


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.
Department of Pediatric Hematology/Oncology, Emory University School of Medicine, Children's Healthcare of Atlanta, AFLAC Cancer Center and Blood Disorders Service, Atlanta, Georgia, USA.
Jeanne E
JE
Hendrickson
John D
JD
Roback
Christopher D
CD
Hillyer
Kirk A
KA
Easley
James C
JC
Zimring
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D017707:Erythrocyte Transfusion / Q000009:adverse effects*; D004912:Erythrocytes / Q000276:immunology*; D005434:Flow Cytometry; D007109:Immunity / Q000187:drug effects; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D011070:Poly I-C / Q000494:pharmacology; D051193:Toll-Like Receptors / Q000819:agonists*
D008070:Lipopolysaccharides; D051193:Toll-Like Receptors; D011070:Poly I-C