Minor histocompatibility antigens on canine hemopoietic progenitor cells

TY - JOUR

T1 - Minor histocompatibility antigens on canine hemopoietic progenitor cells

AU - Weber, Martin

AU - Lange, Claudia

AU - Günther, Wolfgang

AU - Franz, Monika

AU - Kremmer, Elisabeth

AU - Kolb, Hans-Jochem

PY - 2003/6/15

Y1 - 2003/6/15

N2 - 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.

AB - 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.

KW - Animals

KW - Bone Marrow Cells

KW - Cell Division

KW - Cell Lineage

KW - Cells, Cultured

KW - Colony-Forming Units Assay

KW - Dendritic Cells

KW - Dogs

KW - Epitopes, T-Lymphocyte

KW - Female

KW - Hematopoietic Stem Cells

KW - Immunophenotyping

KW - Lymphocyte Culture Test, Mixed

KW - Male

KW - Minor Histocompatibility Antigens

KW - T-Lymphocytes, Cytotoxic

KW - T-Lymphocytes, Regulatory

M3 - SCORING: Journal article

C2 - 12794111

VL - 170

SP - 5861

EP - 5868

JO - J IMMUNOL

JF - J IMMUNOL

SN - 0022-1767

IS - 12

ER -