Lack of antidonor alloantibody does not indicate lack of immune sensitization: studies of graft loss in a haploidentical hematopoietic cell transplantation swine model.
Loss of chimerism is an undesirable outcome of allogeneic hematopoietic cell transplantation (HCT) after reduced-intensity conditioning. Understanding the nature of cellular and humoral immune responses to HCT after graft loss could lead to improved retransplantation strategies. We investigated the immunologic responses after graft loss in miniature swine recipients of haploidentical HCT that received reduced-intensity conditioning. After the loss of peripheral blood chimerism, antidonor cellular responses were present without detectable antidonor antibody. Reexposure to donor hematopoietic cells after graft loss induced a sensitized antidonor cellular response. No induced antidonor antibody response could be detected despite evidence of cellular sensitization to donor cells. In contrast, unconditioned animals exposed repeatedly to similar doses of haploidentical donor cells developed antidonor antibody responses. These results could have important implications for the design of treatment strategies to overcome antidonor responses in HCT and improve the outcome of retransplantation after graft loss.
Department of Surgery, Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts 02129, USA. rduranst@gmail.com
Raimon
R
Duran-Struuck
Abraham
A
Matar
Rebecca
R
Crepeau
Ashley
A
Gusha
Marian
M
Schenk
Isabel
I
Hanekamp
Vimukthi
V
Pathiraja
Thomas R
TR
Spitzer
David H
DH
Sachs
Christene A
CA
Huang
D000818:Animals; D006084:Graft Rejection / Q000276:immunology*; D006239:Haplotypes / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006650:Histocompatibility Testing; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D007114:Immunization; D007518:Isoantibodies / Q000097:blood*; D013552:Swine; D013556:Swine, Miniature; D018183:Transplantation Chimera / Q000276:immunology; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous
D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D007518:Isoantibodies