used to study tolerance to infused
FVIII in hemophilia A mediated by PD-L1+ Tregs
Becker-Gotot J., et
al.
(2022). "Immune tolerance against
infused FVIII in hemophilia A is mediated by PD-L1+ Tregs", J Clin
Invest. 132(22):e159925 https://doi.org/10.1172/JCI159925
Abbreviated
summary:
A
major complication of hemophilia A therapy is the development of alloantibodies
(inhibitors) that neutralize intravenously administered coagulation factor VIII
(FVIII). Immune tolerance induction therapy (ITI) by repetitive FVIII injection
can eradicate inhibitors, and thereby reduce morbidity and treatment costs. It
was shown that immune tolerance against FVIII under nonhemophilic conditions was maintained by
PD-L1–expressing Tregs that ligated PD-1 on FVIII-specific B cells, causing
them to undergo apoptosis. It was shown that PD-1–mediated B cell tolerance
against FVIII operated in healthy individuals and in patients with hemophilia A
without inhibitors, and that ITI reengaged this mechanism.
Figure
ProT2® MHC Class II Tetramer staining of rhFVIII-treated subjects (see Figure 4
in full publication for details https://doi.org/10.1172/JCI159925
ProT2®
MHC Class II Tetramer
Dear
Researchers,
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Key Publications of ProT2® MHC Class II Tetramers
Hartnell F. et al. (2020). Characterising HCV
specific CD4+ T-cells following viral-vectored vaccination, directly acting
anti-virals and spontaneous viral cure. https://doi.org/10.1002/hep.31160
Gliwinski M. et al. (2020). Proinsulin-specific T
regulatory cell may control immune responses in type 1 diabetes: implications
for adoptive therapy. http://dx.doi.org/10.1136/bmjdrc-2019-000873
Cianciotti B. et al. (2019). CD4+ memory stem T cells
recognizing citrullinated epitopes are expanded in patients with rheumatoid
arthritis and sensitive to tumor necrosis factor blockade. https://doi.org/10.1002/art.41157
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