Quantification of the preexisting CD4 T-cell repertoire specific for human erythropoietin reveals its immunogenicity potential.

Abstract:

:Antibody-mediated pure red cell aplasia is a rare but serious event resulting from the induction of neutralizing erythropoietin (Epo)-specific antibodies provoked by treatment with recombinant Epo. Because of the crucial role of CD4 T cells in humoral response, we have quantified the number of Epo-specific CD4 T cells in the blood of normal donors by in vitro stimulation. An important repertoire of preexisting Epo-specific T cells was observed in almost half of the donors, comparable with that of non-self-proteins. This observation suggests that, at the steady state, endogenous Epo weakly contributes to tolerance induction and may be ignored by the immune system. As a result, circulating Epo-specific CD4 T cells could be prone to be activated by altered batches of Epo, providing them with costimulatory signals. Our data also highlight the relevance of T-cell assays performed with normal donors to evaluate the potential immunogenicity of therapeutic proteins.

journal_name

Blood

journal_title

Blood

authors

Delluc S,Ravot G,Maillere B

doi

10.1182/blood-2010-04-280875

subject

Has Abstract

pub_date

2010-11-25 00:00:00

pages

4542-5

issue

22

eissn

0006-4971

issn

1528-0020

pii

blood-2010-04-280875

journal_volume

116

pub_type

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