Minor histocompatibility antigens on canine hemopoietic progenitor cells.
Adoptive immunotherapy with CTL against minor histocompatibility Ags (mHA) provides a promising way to treat leukemia relapse in allogeneic chimeras. Here we describe the in vitro generation of CTL against mHA in the dog. We tested their inhibitory effect on the growth of hemopoietic progenitor cells stimulated by hemopoietic growth factors in a 4-day suspension culture. CTL were produced by coculture of donor PBMC with bone marrow-derived dendritic cells (DCs). These DCs were characterized by morphology, high expression of MHC class II and CD1a, and the absence of the monocyte-specific marker CD14. Characteristically these cells stimulated allogeneic lymphocytes (MLR) and, after pulsing with a foreign Ag (keyhole limpet hemocyanin), autologous T cells. CTL were generated either ex vivo by coculture with DCs of DLA-identical littermates or in vivo by immunization of the responder with DCs obtained from a DLA-identical littermate. In suspension culture assays the growth of hemopoietic progenitor cells was inhibited in 53% of DLA-identical littermate combinations. In canine families mHA segregated with DLA as restriction elements. One-way reactivity against mHA was found in five littermate combinations. In two cases mHA might be Y chromosome associated, in three cases autosomally inherited alleles were detected. We conclude that CTL can be produced in vitro and in vivo against mHA on canine hemopoietic progenitor cells using bone marrow-derived DCs.
Weber
Martin
M
Clinical Cooperative Group Hemopoietic Cell Transplantation, University of Munich, Munich, Germany. m.weber@gsf.de
Lange
Claudia
C
Günther
Wolfgang
W
Franz
Monika
M
Kremmer
Elisabeth
E
Kolb
Hans-Jochem
HJ
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D002455:Cell Division / Q000235:genetics / Q000276:immunology; D019070:Cell Lineage / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000637:transplantation; D004285:Dogs; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D016130:Immunophenotyping; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D015778:Minor Histocompatibility Antigens / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000502:physiology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000637:transplantation; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
D018984:Epitopes, T-Lymphocyte; D015778:Minor Histocompatibility Antigens