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Immune responsiveness against allogeneic platelet transfusions is determined by the recipient's major histocompatibility complex class II phenotype
Author(s) -
Sayeh Ebrahim,
Aslam Rukshana,
Speck Edwin R.,
LeTien Hoang,
Lazarus Alan H.,
Freedman John,
Semple John W.
Publication year - 2004
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.1537-2995.2004.04197.x
Subject(s) - alloimmunity , immunology , major histocompatibility complex , allorecognition , cd8 , biology , mhc class i , antigen , immune system , mhc class ii , antibody
BACKGROUND: Immunoglobulin G (IgG) anti‐platelet (PLT) immunity has been shown to be initiated by indirect allorecognition where recipient T cells recognize donor PLT antigens presented by class II molecules encoded by the major histocompatibility complex (MHC) on recipient antigen‐presenting cells. To understand how the recipient's MHC class II molecules may influence PLT alloimmunity, immune responsiveness against transfused PLTs was tested in different mouse strains. STUDY DESIGN AND METHODS: Various inbred and mutant mouse strains were transfused with allogeneic PLTs and IgG donor antibodies were measured by flow cytometry. RESULTS: When recipient mice, expressing both MHC class II I‐A and MHC class II I‐E molecules, were transfused weekly with allogeneic PLTs, high titers of IgG donor antibodies were generated. In comparison, however, recipient mice expressing only MHC class II I‐A molecules had significantly (p < 0.001) reduced IgG antibody responsiveness against PLT transfusions. The low IgG responder status against allogeneic PLT transfusions was rescued in transgenic mice expressing I‐E molecules and in mice genetically deficient in either β 2 ‐microglobulin or CD8+ T cells. CONCLUSION: IgG immune responsiveness against allogeneic PLT transfusions is dependent on recipient expression of I‐E MHC class II molecules, whereas I‐A expression is linked with CD8‐mediated suppression of PLT immunity. The data suggest that strategies to modify recipient MHC class II presentation of donor PLT antigens would be effective in eliminating PLT alloimmunity.