Transfused platelets enhance alloimmune responses to transfused KEL-expressing red blood cells in a murine model.
Blood Transfus
; 17(5): 368-377, 2019 09.
Article
em En
| MEDLINE
| ID: mdl-30418129
ABSTRACT
BACKGROUND:
Factors influencing the development of alloantibodies against blood group antigens on transfused red blood cells are poorly defined. We hypothesised that transfused platelets may act as a danger signal to recipients and affect humoral immune responses to transfused red blood cells. MATERIALS ANDMETHODS:
Platelet-rich plasma prepared from wild-type C57BL/6 or CD40L knock-out donors was transfused into wild-type or CD40L knock-out recipients. Leucoreduced red blood cells from transgenic donors expressing high levels of the human KEL glycoprotein in an erythrocyte-specific manner (KELhi donors) were transfused after the platelets, and anti-KEL responses were measured longitudinally. In some experiments, recipients were treated with poly (IC), monoclonal CD40L-blocking antibody, or CD4-depleting antibody prior to transfusion.RESULTS:
Transfusion of wild-type C57BL/6 platelets or treatment with poly (IC) prior to KELhi red blood cell transfusion led to an anti-KEL alloimmune response in wild-type recipients. Transfusion of platelets from wild-type but not CD40L knock-out donors prior to KELhi red blood cell transfusion led to an IgG anti-KEL alloimmune response in CD40L knock-out recipients; unexpectedly, transfusion of platelets from CD40L knock-out donors prior to KELhi red blood cell transfusion led to a robust anti-KEL alloimmune response in wild-type recipients. Recipient treatment with MR1 CD40L-blocking antibody or CD4-depleting antibody prevented KEL alloimmunisation altogether.DISCUSSION:
Transfused platelets serve as an adjuvant in this T-dependent murine model of anti-KEL red blood cell alloimmunisation, with CD40/CD40L interactions being involved to some degree but with additional mechanisms also playing a role. These findings raise questions about the role that transfused or endogenous platelets may play in other innate/adaptive immune responses.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Plaquetas
/
Glicoproteínas de Membrana
/
Metaloendopeptidases
/
Transfusão de Plaquetas
/
Transfusão de Eritrócitos
/
Eritrócitos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article