Tolerance in DLA-haploidentical canine littermates following CD6-depleted marrow transplantation and donor lymphocyte transfusion.
OBJECTIVE
Donor lymphocyte transfusions (DLT) are effective in the treatment of leukemia after allogeneic stem cell transplantation. Graft-vs-host-disease (GVHD) is the major risk factor of DLT. In dog leukocyte antigen (DLA)-identical littermate dogs, DLT given within 3 weeks after transplantation of marrow depleted of T cells using absorbed antithymocyte globulin produced fatal GVHD, whereas at 2 months or later after transplantation, DLT were tolerated without GVHD. Here, we studied tolerance to DLT in DLA-haploidentical recipients of CD6-depleted bone marrow.


METHODS
Bone marrow recipients were DLA-heterozygous and DLA-haploidentical to their DLA-homozygous donors. Marrow transplantation was performed on day 0, one day after total body irradiation with 10Gy. CD6 depletion was achieved by treatment of the marrow with CD6 antibody and rabbit complement. Natural killer cell activity of CD6-depleted cells was studied against canine thyroid adenocarcinoma cells. DLT were given at various time points after transplantation.


RESULTS
Seven DLA-heterozygous dogs given undepleted marrow died of GVHD within 28 days. In contrast, three dogs given CD6-depleted marrow had sustained engraftment without occurrence of GVHD. DLT given on either day 3, 7, or 14 produced fatal GVHD. DLT on day 20, however, produced fatal GVHD in only two of four dogs. Mixed chimerism was converted into complete chimerism in all cases. Contrary to T-cell depletion with antithymocyte globulin, CD6 depletion spares canine natural killer cells.


CONCLUSIONS
We conclude that T-cell depletion with CD6 antibody and complement induces graft-vs-host tolerance without jeopardizing engraftment. DLT on days 3, 7, and 14 after transplantation produced GVHD, but it failed to abrogate tolerance in two of four dogs transfused on day 20.
Zorn
Julia
J
Helmholtz Zentrum München, National Research Center for Environmental Health, Institute of Molecular Immunology, Clinical Cooperation Group Hematopoietic Cell Transplantation, Munich, Germany.
Herber
Martin
M
Schwamberger
Sabine
S
Panzer
Werner
W
Adler
Heiko
H
Kolb
Hans-Jochem
HJ
D000818:Animals; D000831:Animals, Newborn; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D016026:Bone Marrow Transplantation / Q000379:methods*; D045744:Cell Line, Tumor; D004285:Dogs; D006239:Haplotypes; D015395:Histocompatibility Antigens Class I; D007108:Immune Tolerance; D007694:Killer Cells, Natural / Q000276:immunology; D008212:Lymphocyte Depletion; D017710:Lymphocyte Transfusion; D013964:Thyroid Neoplasms / Q000473:pathology; D014181:Transplantation Immunology; D014184:Transplantation, Homologous; D014916:Whole-Body Irradiation
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; C062279:CD6 antigen; D015395:Histocompatibility Antigens Class I; C039692:histocompatibility antigen DLA