title: T and B cell responsiveness to donor class I MHC molecules and peptides in long survivors with kidney allografts.
abstract: LEW rats with long-surviving (> 100 days) (DA x LEW)F1 kidney allografts were generated by treating the recipients with cyclosporine for 14 days after grafting. All rats were monitored after transplantation for the development of antibodies to intact donor class I MHC molecules. Cyclosporine completely suppressed the early antibody response to intact DA class I MHC molecules in all 19 LEW rats. However, 17 of the 19 rats developed antibodies between four and six weeks after grafting-i.e., between two and four weeks after the cessation of cyclosporine therapy, and maintained high levels of antibody to the donor class I molecules in spite of the long-term presence of the allograft. The 2 rats that did not produce antibodies to donor class I MHC molecules, along with one of the 17 that did produce antibodies, were immunized with a synthetic peptide corresponding to a region of the DA class I MHC molecule known to be recognized by LEW CD4+ T cells via the indirect recognition pathway. All 3 long survivors developed self APC-dependent CD4+ T cell proliferation to the immunizing donor peptides, and strong antibody responses to these peptides. However, none of these long survivors suffered rejection episodes as a consequence of the peptide immunization. In one of the two long-surviving rats without antibodies to intact donor class I MHC molecules at the time of peptide priming, the peptide priming resulted in the prompt development of strong antibodies to intact donor class I molecules. However, the other of these 2 rats did not produce such antibodies after peptide priming. Thus in this model of kidney allograft tolerance, with long-term exposure of the recipient's immune system to donor antigens without evidence of rejection, none of the animals develops tolerance for the indirect T cell recognition of donor class I MHC antigens. In occasional animals, B cells potentially reactive to intact donor class I molecules are present and are adequately exposed to antigen but are quiescent because of the absence of T cell help, perhaps as a consequence of reversible T cell suppression or anergy. In other occasional animals, B cell nonreactivity (anergy or tolerance) to intact donor class I molecules appears to develop.
authors.affiliation: Division of Cell and Molecular Biology, Institute of Child Health, University of London, United Kingdom.
authors.forename: A m
authors.initials: Am
authors.lastname: Benham
authors.forename: G J
authors.initials: GJ
authors.lastname: Sawyer
authors.forename: J W
authors.initials: JW
authors.lastname: Fabre
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D007108:Immune Tolerance; D007518:Isoantibodies / Q000096:biosynthesis; D016030:Kidney Transplantation / Q000276:immunology*; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D011919:Rats, Inbred Strains; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D015395:Histocompatibility Antigens Class I; D007518:Isoantibodies; D010455:Peptides