INDIRECT T-CELL ALLORECOGNITION OF DONOR ANTIGENS CONTRIBUTES TO THE REJECTION OF VASCULARIZED KIDNEY ALLOGRAFTS

被引:66
作者
BENHAM, AM [1 ]
SAWYER, GJ [1 ]
FABRE, JW [1 ]
机构
[1] UNIV LONDON,INST CHILD HLTH,DIV CELL & MOLEC BIOL,TRANSPLANTAT BIOL UNIT,LONDON WC1N 1EH,ENGLAND
关键词
D O I
10.1097/00007890-199504150-00019
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
This report demonstrates for the first time that indirect T cell allorecognition of donor antigens can contribute to the effector mechanism of rejection of vascularized organ allografts. LEW (RT1(l)) rats were primed for indirect T cell allorecognition of DA (RT1(avl)) classical class I MHC molecules by immunization with synthetic 22-24 amino acid peptides corresponding to the alpha-helices of the RT1-A class I molecule. These rats received (DA x LEW) F-1 kidney grafts that had been depleted of donor interstitial dendritic cells to minimize the direct T cell allorecognition response to the graft. The peptide-immunized rats rejected their grafts more rapidly than did control immunized rats, in terms of both graft function and survival. Moreover, the kinetics of antibody production to intact donor class I molecules after kidney transplantation was much more rapid in the peptide-immunized rats, suggesting that T cell help is the rate-limiting factor for antibody production to donor antigens in this model. It was of interest that we could not detect an antibody response to donor peptides after kidney graft rejection.
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页码:1028 / 1032
页数:5
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  • [1] Fangmann J., Dalchau R., Fabre J.W., Rejection of skin allografts by indirect allorecognition of donor class 1 major histocompatibility complex peptides, J Exp Med, 175, (1992)
  • [2] Dalchau R., Fangmann J., Fabre J.W., Allorecognition of isolated denatured chains of class I and class II MHC molecules. Evidence for an important role for indirect allorecognition in transplantation, Eur J Immunol, 22, (1992)
  • [3] Auchincloss H., Lee R., Shea S., Markowitz J.S., Grusby M.J., Glimcher L.H., The role of "indirect" recognition in initiating rejection of skin grafts from major histocompatibility complex class II deficient mice, Proc Natl Acad Sci USA, 90, (1993)
  • [4] Benichou G., Takizawa P.A., Olson C.A., McMillan M., Sercarz E.E., Donor major histocompatibility complex (MHC) peptides are presented by recipient MHC molecules during graft rejection, J Exp Med, 175, (1992)
  • [5] Fangmann J., Dalchau R., Sawyer G.J., Priestley C.A., Fabre J.W., T cell recognition of donor major histocompatibility complex class I peptides during allograft rejection, Eur J Immunol, 22, (1992)
  • [6] Liu Z., Yu-Kai S., Yu-Ping X., Et al., Contribution of direct and indirect recognition pathways to T cell alloreactivity, J Exp Med, 177, (1993)
  • [7] Lechler R.I., Batchelor J.R., Restoration of immunogenicity to pas senger cell-depleted kidney allografts by the addition of donor strain dendritic cells, J Exp Med, 155, (1982)
  • [8] Rada C., Lorenzi R., Powis S.J., Bogaerde J., Parham P., Howard J.C., Concerted evolution of class I genes in the major histocompatibility complex of murine rodents, Proc Natl Acad Sci USA, 87, (1990)
  • [9] Fabre J.W., Lim S.H., Morris P.J., Renal transplantation in the rat, Aust N Z J Surg, 41, (1971)
  • [10] Dalchau R., Fabre J.W., Identification and unusual distribution of the canine and human homologues of Thy-1 (θ), J Exp Med, 149, (1979)