Mechanism of hyporesponsiveness caused by donor-specific transfusion to allogeneic minor antigens.
Donor-specific transfusion (DST) is one of the methods to prevent allograft rejection, presumably through induction of donor-specific nonresponsiveness in humans and animal models. In this study, we used a skin graft model in fully allogeneic (AKR into B6), H-2 class I-disparate (bm1 into B6), class II-disparate (bm12 into B6), minor-H-disparate (C3H/SW into B6) and whole MHC-disparate (B10.BR into B10) combinations to analyze the mechanisms of DST-induced immunomodulation from the view point of antigen disparity. Skin graft survival was prolonged by DST only in the combination of bm1 and B6 as already confirmed by many reports. In other combinations, skin graft survivals were not prolonged at all by DST but rather shortened. In a fully allogeneic combination between AKR and B6 in which I-E antigens or Mls-1 antigens are recognized by T-cell subsets with TCR Vbeta11 or Vbeta6, respectively, responses to stimulation by anti-Vbeta11 and Vbeta6 monoclonal antibodies were decreased by DST. Furthermore, the number of Vbeta6+ T cells was decreased in the periphery probably due to peripheral clonal deletion. In such a condition, the mixed lymphocyte reactions of B6 to AKR were reduced to some extent, but were clearly detected. In addition, skin allografts from AKR were more rapidly rejected in B6 mice given AKR spleen cells. From these results, DST seems to induce nonresponsiveness to some antigens (I-E antigens, Mls antigens and bm1 antigens in this study), but not to others. Our study also indicated that DST alone, at least in the absence of other treatments, does not contribute to allograft tolerance in fully allogeneic combinations.
Nomoto
K
K
First Department of Surgery, Gunma University, Maebashi, Japan.
Kanoh
K
K
Suzuki
H
H
Shimura
T
T
Kuwano
H
H
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001803:Blood Transfusion; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D006084:Graft Rejection / Q000517:prevention & control*; D006085:Graft Survival; D007519:Isoantigens / Q000276:immunology*; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008815:Mice, Inbred Strains; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis / Q000276:immunology; D016038:Skin Transplantation / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000502:physiology; D013950:Thymus Gland / Q000502:physiology; D014019:Tissue Donors; D018183:Transplantation Chimera; D019172:Transplantation Conditioning / Q000379:methods*
D000911:Antibodies, Monoclonal; D007519:Isoantigens; D016693:Receptors, Antigen, T-Cell, alpha-beta