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Semaphorin 3 A alters endothelial cell immunogenicity by regulating C lass II transactivator activity circuits
Author(s) -
Schlahsa Laura,
Zhang HaiJiao,
Battermann Anja,
Verboom Murielle,
Immenschuh Stephan,
EizVesper Britta,
Stripecke Renata,
Engelmann Katrin,
Blasczyk Rainer,
Figueiredo Constança
Publication year - 2014
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/trf.12631
Subject(s) - ciita , immunogenicity , transplantation , biology , transactivation , semaphorin , microbiology and biotechnology , receptor , green fluorescent protein , stimulation , immune system , cancer research , immunology , t cell , gene expression , endocrinology , medicine , gene , genetics , mhc class ii
Background Endothelial cells ( EC s) play a pivotal role in the allogeneic immune response upon transplantation. Semaphorin 3 A ( S ema3 A ) was implicated in the modulation of EC growth, but its effects on immunogenicity were not previously investigated. Study Design and Methods EC s were transduced with a lentiviral vector encoding for the green fluorescence protein ( GFP ) sequence under the control of a C lass II transactivator ( CIITA )‐dependent promoter. Upon stimulation of nonmodified EC s with recombinant S ema3 A protein, mRNA and protein levels of CIITA , HLA ‐ DR , and S ema3 A receptors were evaluated. An enzyme‐linked immunosorbent assay was developed to quantify S ema3 A levels in the sera of kidney‐transplanted patients. Results S ema3 A stimulation of lentiviral vector encoding for the GFP sequence EC s caused a significant up regulation of the transgene expression, indicating an increase in CIITA levels. Stimulation of nonmodified EC s with S ema3 A resulted in an up regulation of CIITA expression, which was associated with enhanced HLA ‐ DR levels and an increase in alloreactive CD 4+ T ‐cell proliferation. S ema3 A receptor expression was enhanced by CIITA , establishing a positive feedback loop. Higher levels of S ema3 A were observed in sera of patients presenting with organ rejection. Conclusion This study links S ema3 A signaling in EC s with increased CIITA levels and higher HLA ‐ DR expression, resulting in CD 4+ T ‐cell activation, which might have important implications for tissue and organ transplantation.