Gene therapy with IgG-HY fusion proteins to reduce male-specific T-cell reactivity in vitro

Miranda P. Dierselhuis, Ellen Schrama, David W. Scott, Eric Spierings

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

5 Citaten (Scopus)


Graft-versus-host disease is still a major complication in stem-cell transplantation. In HLA-identical stem-cell transplantation, mismatches in minor histocompatibility antigens contribute to the development of graft-versus-host disease. As treatment of graft-versus-host disease with immunosuppressive drugs potentially also reduces the graft-versus-leukemia responses, antigen-specific tolerance induction may be used to reduce graft-versus-host disease while leaving the graft-versus-leukemia responses intact. In mouse models, induction of antigen-specific tolerance using IgG-antigen-transduced B cells can prevent and ameliorate autoimmunity. In this study, the principle of the in vivo animal model has been applied to a human in vitro model wherein induction of tolerance against the HLA class II-restricted male-specific minor histocompatibility antigen RPS4Y1 has been analyzed. T cells precultured in the presence of B cells expressing the IgG-coupled HY antigen showed reduced responsiveness selectively against the minor HY antigen RPS4Y1 in different in vitro protocols. These first observations serve as a basis for further studying and understanding the tolerizing potential of IgG constructs with human T cells.

Originele taal-2Engels
Pagina's (van-tot)44-54
Aantal pagina's11
TijdschriftHuman Gene Therapy
Nummer van het tijdschrift1
StatusGepubliceerd - 1 jan. 2011
Extern gepubliceerdJa


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