Quantification of the preexisting CD4 T-cell repertoire specific for human erythropoietin reveals its immunogenicity potential.
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.
Delluc
Stéphanie
S
Protéus, Nimes, France.
Ravot
Gilles
G
Maillere
Bernard
B
D057134:Antibodies, Neutralizing / Q000009:adverse effects / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D004921:Erythropoietin / Q000009:adverse effects / Q000276:immunology*; D006801:Humans; D011994:Recombinant Proteins; D012010:Red-Cell Aplasia, Pure / Q000209:etiology / Q000276:immunology
D057134:Antibodies, Neutralizing; D011994:Recombinant Proteins; D004921:Erythropoietin