Prevention of graft-versus-host disease in DLA-haplotype mismatched dogs and hemopoietic engraftment of CD6-depleted marrow with and without cG-CSF treatment after transplantation.
Prevention of graft-versus-host disease by depletion of CD6-positive T cells was studied in the dog. Donors were DLA-homozygous, recipients DLA-heterozygous with one DLA haplotype identical to the donor. Seven control dogs received untreated marrow and died of GvHD after full hemopoietic recovery within 28 days of transplantation. For prevention of GvHD, immunomagnetic separation of T cells with a monoclonal antibody against human CD6 that crossreacted with canine T cells was evaluated. Depletion of CD6-positive cells depleted CD4-positive cells completely, but only part of CD8-positive cells and DR-positive cells. CD6-depleted marrow exhibited strong nonspecific "natural" suppression of the generation of cytotoxic T cells in vitro. Eleven dogs received CD6-depleted marrow. Only 1 dog developed GvHD and died. Sustained engraftment was seen in 8 dogs. Hemopoietic recovery was delayed and slower after transplantation of CD6-depleted marrow than after transplantation of untreated marrow. Four of these dogs were treated with G-CSF, and this accelerated the recovery of leukocytes, but did not prevent rejection. Chimerism was mixed in 7 of 10 evaluable dogs and 1 dog recovered its own hemopoiesis 2 years after transplantation. CD6 depletion prevents GvHD across a DLA-haplotype difference, but rejection and mixed chimerism may occur. Treatment with G-CSF accelerates leukocyte recovery, but cannot prevent rejection.
Schumm
M
M
GSF-Forschungszentrum für Umwelt, Ludwig-Maximilians-Universität München, Germany.
Günther
W
W
Kolb
H J
HJ
Rieber
P
P
Büttner
M
M
Voss
C
C
Kremmer
E
E
Reitmeier
P
P
Thierfelder
S
S
Wilmanns
W
W
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D015703:Antigens, CD / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D016026:Bone Marrow Transplantation / Q000009:adverse effects / Q000276:immunology*; D003114:Colony-Forming Units Assay; D004285:Dogs / Q000276:immunology*; D005260:Female; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000517:prevention & control*; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D006239:Haplotypes / Q000235:genetics; D006410:Hematopoiesis; D006649:Histocompatibility Antigens / Q000235:genetics / Q000276:immunology*; D015395:Histocompatibility Antigens Class I; D007155:Immunologic Factors / Q000627:therapeutic use*; D008212:Lymphocyte Depletion; D008297:Male; D011828:Radiation Chimera / Q000276:immunology; D016038:Skin Transplantation / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; C062279:CD6 antigen; D006649:Histocompatibility Antigens; D015395:Histocompatibility Antigens Class I; D007155:Immunologic Factors; C039692:histocompatibility antigen DLA; D016179:Granulocyte Colony-Stimulating Factor