Gene therapy with IgG-HY fusion proteins to reduce male-specific T-cell reactivity in vitro.
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.
Dierselhuis
Miranda P
MP
Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.
Schrama
Ellen
E
Scott
David W
DW
Spierings
Eric
E
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D002460:Cell Line; D005260:Female; D015316:Genetic Therapy; D006086:Graft vs Host Disease / Q000276:immunology; D006182:H-Y Antigen / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D007074:Immunoglobulin G / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D015778:Minor Histocompatibility Antigens / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use; D033581:Stem Cell Transplantation; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
D006182:H-Y Antigen; D000949:Histocompatibility Antigens Class II; D007074:Immunoglobulin G; D015778:Minor Histocompatibility Antigens; D011993:Recombinant Fusion Proteins