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Biomedical subjects

H Auchincloss

Publications and source records attributed to H Auchincloss.

At least 91 records · Page 5Linked to original sources
PubMed1989

Procurement of a whole pancreas and liver from the same cadaveric donor.

Analogous arterial and portal circulation to the liver and pancreas has heretofore represented an impediment to the simultaneous procurement of a liver and pancreas from the same cadaveric donor. A surgical approach that allows for the retention of sufficient arterial and portal supply to both allografts is described. Variant hepatic arterial anatomy may be technically managed by the use of a donor iliac artery interposition graft.

Adolescent↗
PubMed1988

Effects of in vivo administration of anti-T3 monoclonal antibody on T cell function in mice. I. Immunosuppression of transplantation responses.

Anti-T3 mAb are being increasingly used clinically in the treatment of organ graft rejection. However, there has not previously been a murine model in which the effects of these mAb on the immune system could be studied in vivo. We have established such a model using the anti-murine-T3 mAb, 145-2C11. Administration of 145-2C11 led to rapid depletion of T cells from peripheral blood and suppression of skin graft rejection. However, depletion of T cells from spleen and lymph node was both delayed and incomplete. Full recovery of T cell number was dependent on the presence of a thymus, but treatment of thymectomized animals revealed that depletion was not the mechanism by which the mAb induced immunosuppression. Rather, alterations in TCR expression may play a more important role. TCR had modulated from T cells in spleen and lymph node early after treatment, and TCR expression remained subnormal for at least 51 days posttreatment. However, subnormal TCR expression alone could not fully explain the observed T cell dysfunction, inasmuch as a period of time existed after TCR re-expression during which T cells appeared to be anergic to CTL and MLR reactivity. These findings implicate T cell dysfunction as an important element in the induction of immunosuppression after anti-T3 administration.

Animals↗
PubMed1988

Combined kidney and pancreas transplantation in diabetics.

Kidney and pancreaticoduodenal transplantation were simultaneously performed in 12 insulin-dependent diabetic patients. These patients had advanced secondary complications, including blindness, vascular disease, and disabling neuropathy. Average posttransplant hospitalization and charges were 17.7 days and $42,780 compared with 11.2 days and $29,000 for patients who received renal allografts alone. Following transplantation, blood glucose and glycosylated hemoglobin A levels promptly returned to normal in all patients. Two patients subsequently died, one after five months of a cytomegalovirus infection and one after seven months of a ruptured bladder. After a mean of 11.6 months of follow-up, ten patients (83%) remained independent of insulin and dialysis. The success of pancreas transplantation in diabetics with advanced complications now approaches that of other organ allografts. It therefore appears reasonable to recommend transplantation for diabetics with less severe secondary complications, since these candidates are most likely to realize the potential benefits of long-term normoglycemia.

Adult↗
PubMed1988

Prevention of alloantibody formation after skin grafting without prolongation of graft survival by anti-L3T4 in vivo.

Treatment of mice in vivo with monoclonal antibodies against the L3T4 antigen (CD4 in human beings) has been shown to suppress the humoral response to several foreign antigens and to prolong the survival of allografts in some cases. Experiments were therefore performed to test whether anti-L3T4 antibody treatment would suppress alloantibody production after skin transplantation. Monoclonal anti-L3T4 antibody (GK1.5) was administered to C57BL/6 (B6) mice prior to BALB/c skin grafting. The production of B6 anti-BALB/c alloantibody was then tested after graft rejection. The results showed that: (1) graft survival of BALB/c skin on B6 mice was not substantially prolonged by anti-L3T4 treatment; (2) graft survival was significantly prolonged if mice were treated with both anti-L3T4 and anti-Lyt2 antibody; (3) the production of alloantibody following grafting was decreased by anti-L3T4 treatment and was completely eliminated if thymectomy was also performed; (4) thymectomy prolonged the effectiveness of the anti-L3T4 treatment; (5) tolerance to alloantigens presented at the time of anti-L3T4 treatment was not achieved; and (6) well-established cytotoxic antibody titers rose to higher levels after secondary grafting even with concurrent anti-L3T4 treatment, while weak antibody titers remained stable or decreased. These results indicate that L3T4+ cells are essential in providing the "help" necessary for generating humoral responses to alloantigens but that elimination of these L3T4+ cells still allows the generation of help for cell-mediated immunity. The data also suggest that class I antigens must be presented on class II molecules in order to elicit an antibody response.

Animals↗
PubMed1987

The selective use of antilymphocyte serum for cyclosporine treated patients with renal allograft dysfunction.

Eighty-seven adult renal allograft recipients were initially treated with cyclosporine-prednisone immunosuppression. Thirty patients experienced no episode of rejection. Antilymphocyte antibody therapy (ALS) was administered to 21 of the 68 recipients of cadaveric donor allografts for either primary allograft dysfunction or acute rejection, and to 6 of 19 recipients of haploidentical, living-related allografts because of steroid-resistant rejection. The cumulative allograft and patient survival for the entire series (follow-up 9-36 months) was 84% and 95%, respectively. This improvement in the rate of successful transplantation can be attributed to the selective addition of ALS therapy to recipients with specific instances of renal allograft dysfunction. In this report, the indications for the use of ALS preparations following prophylactic CsA immunosuppression are reviewed. Experience with the protocols of the ALS administration is also discussed. In selected cases, the administration of either ATG or OKT3 can significantly benefit CsA recipients who experience either primary allograft nonfunction or an epidose of acute rejection.

Administration, Oral↗
PubMed1984

Effect of class II antigen matching on renal allograft survival in miniature swine.

The benefit of class II major histocompatibility complex (MHC) antigen matching to renal allograft survival, in the absence of immunosuppression, has been studied in partially inbred miniature swine. Permanent (greater than 6 mo) renal allograft survival was found in 30% of recipients of either class II only or fully matched grafts. Analysis of the survival of the class II-only matched grafts by specific recipient/donor haplotype combinations indicated that survival was regulated by at least three genetic factors, including antigen gene dose, a class I MHC allele-dependent effect, and non-MHC-linked immune response phenomenon. Animals accepting class II-matched kidneys developed spontaneous tolerance to the graft, despite mounting an initial immune response marked by renal damage and the development of serum cytotoxic antibodies directed at the donor MHC antigens. The antibodies were only of the IgM class, suggesting that conversion of the humoral response to IgG was blocked. After acceptance of the kidney, three out of five animals showed specific prolongation of donor skin grafts. At the time of rejection of these skin grafts, no decrease in renal function nor reappearance of anti-donor antibodies was observed.

Animals↗
PubMed1984

Immunologic characterization of MHC recombinant swine: role of class I and II antigens in in vitro immune responses.

A recombinant haplotype between the class I and class II major histocompatibility loci of inbred miniature swine has made it possible to study the role of the corresponding antigens in in vitro and in vivo immune responses. Before examining the effects of selective SLA locus matching on allograft survival, it was deemed necessary to determine the corresponding effects on in vitro parameters of immunity. The results presented in this paper indicate that: (1) a difference at the class II loci was required for a maximal proliferative response; (2) class I antigen differences alone led to a slight proliferative response which depended on the haplotype combination used; (3) in cell-mediated cytoxicity assays, the class I antigens were found to be the primary targets for lysis. Although optimal CTL generation required the presence of both class I and class II antigen differences, CTL were sometimes generated in the absence of a known class II difference. The weak, intermittent cytotoxicity seen in these cultures of class II matched cells could be augmented by the addition of third party, class I matched, class II mismatched, stimulator cells. Taken together, these data provide evidence for the conservation of function of antigen class between species. They also provide further evidence for the two-signal hypothesis of CTL generation. Thus, MHC recombinant swine provide a model for the study of the effect of antigen class on in vitro and in vivo immunobiology.

Animals↗
PubMed1983

Antiidiotypes against anti-H-2 monoclonal antibodies. V. In vivo antiidiotype treatment induces idiotype-specific helper T cells.

Mice have been treated in vivo with xenogeneic antiidiotypes prepared against a murine monoclonal anti-H-2Kk antibody, 11-4.1. B cell immune responses have been found to be altered by such treatment as evidenced by a modification in the idiotypic repertoire of the humoral response to H-2 antigens. Transfer of purified T cells into nude mice before anti-idiotype treatment showed that T cells are involved in the induction of idiotope-bearing antibodies by xenogeneic antiidiotype. Studies using bone marrow chimeras indicate that the environment in which either T or B cells mature does not appear to alter VH region genetic control of induction of antiidiotype-induced molecules. By adoptive transfer studies, T cells from antiidiotype-treated mice were found capable of modifying the idiotypic repertoire of B cells subsequently exposed to antigen even when the T cells were obtained from antiidiotype-primed mice of inappropriate allotype. Although it still must be determined whether idiotypic or antiidiotypic T cells are involved in such B cell idiotype regulation, these results indicate that some T cell functions are altered by xenogeneic antiidiotypes prepared against B cell products and suggest that T cell immunity to major histocompatibility complex antigens may also be affected by such reagents.

Animals↗
PubMed1983

Anti-idiotypes against anti-H-2 antibodies VI. Detection of shared idiotypes among monoclonal anti-H-2 antibodies.

Anti-idiotypes produced against monoclonal anti-H-2 antibodies have been used to examine idiotope sharing among a panel of anti-major histocompatibility complex (MHC) antibodies detecting the same and different specificities. Both xenogeneic anti-100-30 and anti-3-83, which did not react with predominant idiotypes in conventional alloantisera, detected idiotopes on 3-83 and 100-30 as well as on 2 other monoclonal anti-H-2Kk antibodies. All 4 monoclonal antibodies recognized the same epitope cluster on the Kk molecule and detected the same serological specificity. H-2.5. In contrast, syngeneic and allogeneic anti-idiotype produced against the same monoclonal antibodies did not detect these cross-reactive determinants. In several instances, xenogeneic anti-idiotype reacted with anti-MHC antibodies which recognized distinct H-2 determinants, suggesting that anti-MHC antibodies detecting the same or different specificities may share idiotypic determinants. These reagents may be useful probes of the anti-MHC immune repertoire.

Animals↗
PubMed1983

Mechanisms of tolerance in murine radiation bone marrow chimeras. I. Nonspecific suppression of alloreactivity by spleen cells from early, but not late, chimeras.

Allogeneic chimeras were prepared using lethally irradiated B6 hosts and untreated marrow from exsanguinated BALB/c donors. For about two months after reconstitution, chimeras had very weak antihost cell-mediated lymphocytotoxicity (CML) reactivity and little third-party alloreactivity. During this time a cell population capable of suppressing CML reactivity against both host and third-party alloantigens (i.e., antigen-nonspecific) was demonstrated in chimera spleens by in vitro mixing experiments. The putative suppressor cells were Thy-1-negative and radiation-sensitive. Subsequently, mature chimeras showed host tolerance and strong third-party alloreactivity. At this point suppressor mechanisms could no longer be demonstrated. These data are consistent with a clonal elimination hypothesis in that they do not provide evidence to indicate that maintenance of specific immune tolerance is mediated by an active suppressor mechanism.

Animals↗
PubMed1983

Mechanisms of tolerance in murine radiation bone marrow chimeras. II. Absence of nonspecific suppression in mature chimeras.

Spleen cells from a series of allogeneic bone marrow chimeras were sensitized in vitro with stimulator cells from major histocompatibility complex recombinant strains of mice. The combinations were chosen such that both tolerated (host or donor) and nontolerated (third-party) antigens were present on the same stimulator cells in order to determine whether the tolerated host antigens might elicit nonspecific suppressor mechanisms affecting the cell-mediated lympholysis (CML) response to the nontolerated antigens. No evidence for such nonspecific suppression was obtained in several types of assays. Therefore, if suppressor mechanisms exist that mediate such tolerance in mature allogeneic chimeras then these mechanisms must be highly antigen-specific.

Animals↗
PubMed1982

Anti-idiotypes against anti-H-2 monoclonal antibodies: structural analysis of the molecules induced by in vivo anti-idiotype treatment.

Previous studies have shown that treatment of mice in vivo with xenogeneic anti-idiotype produced against a monoclonal anti-H-2Kk antibody, 11-4.1, leads to the induction of molecules (Id') that inhibit the binding of anti-idiotype to idiotype. To investigate the nature of these Id' molecules, spleens from such anti-idiotype-treated mice were fused with the SP2/0 myeloma to produce monoclonal Id' antibodies. All four monoclonal Id' antibodies were found to react with goat and rabbit anti-11-4.1 in addition to the pig anti-idiotype used for their induction and one of the four, J1-8-1, reacted with syngeneic BALB/c anti-11-4.1. Partial amino acid sequences were determined for the heavy and light chains of these monoclonal antibodies. J1-8-1 heavy chain had an NH2-terminal amino acid sequence identical to that of 11-4.1 for the 39 NH2-terminal residues assigned, whereas its light chain and the heavy and light chains of the other Id' molecules differed markedly from those of the 11-4.1 antibody. Isolated heavy chains and light chains of J1-8-1 and 11-4.1 were reassociated in homologous and heterologous pairs. When J1-8-1 heavy chains and 11-4.1 light chains were mixed in equimolar concentrations, anti-H-2Kk reactivity was found at a level approximately 10% of that observed for reassociated 11-4.1 homologous heavy and light chains. The finding that in vivo anti-idiotype treatment can trigger Id' molecules structurally similar to the original idiotype has implications regarding the mechanism of induction of Id' molecules and the regulation of repertoire expression by idiotypic networks.

Amino Acid Sequence↗
PubMed1982

A monoclonal antibody detecting unusual Thy-1 determinants.

20-10-5S is a monoclonal antibody produced by the fusion of C3H anti-C3H.SW splenocytes with the SP2/0 cell line. The antibody appears to react with Thy-1 determinants by several criteria including cytotoxicity patterns, functional assays, genetic analyses, and competitive binding experiments. However, the antibody and the determinants it detects are unusual in that: 1) 20-10-5S is autoreactive; 2) the antibody shows allospecificity for Thy-1.2 vs Thy-1.1 antigens only on peripheral lymphocytes and not on thymocytes; and 3) the antibody reacts only with determinants on murine T cells and not with antigens on brain tissue or on rat thymocytes. It therefore seems that 20-10-5S reacts with murine T cell-specific Thy-1 determinants that are lost or modified during maturation of the cells on which they are expressed.

Animals↗