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W J Burlingham

Publications and source records attributed to W J Burlingham.

69 records · Page 4Linked to original sources
PubMed1987

Human fetal pancreas--a potential source for transplantation.

Human fetal pancreas (HFP) represents an ideal tissue source for transplantation into diabetic patients. Transplantation of HFP lacks many of the technical problems associated with whole organ transplantation and HFP is readily available. In order to proceed with clinical HFP transplantation it must be demonstrated that HFP can reverse experimentally induced diabetes, that HFP can respond to glucose challenge in a manner similar to adult tissue, and that the immunogenicity of HFP can be reduced. We transplanted HFP (13-17 weeks gestational age) beneath the kidney capsule of streptozotocin-induced diabetic BALB/c nu/nu mice. Within 6 to 8 weeks following transplantation, 6 out of 7 (88%) animals became normoglycemic. Oral glucose tolerance tests were performed to determine in vivo graft function. Results in cured animals were identical to those of normal BALB/c nu/nu mice. In vitro insulin response to glucose challenge demonstrated that grafted HFP was capable of insulin secretion in the presence of high glucose while fresh fetal tissue was not. Human passenger leukocytes, identified immunohistologically at various times after transplantation with monoclonal antibodies to HLA-DR and Leu 10, were greatly reduced by 32 weeks posttransplant. Our data demonstrate that HFP will differentiate and mature in the diabetic nude mouse and that human passenger leukocyte content can be reduced. These findings suggest that HFP is functionally suitable for transplantation into diabetic patients.

Animals↗
PubMed1987

Improved renal allograft survival following donor-specific transfusions. II. In vitro correlates of early (DST-type) rejection episodes.

Early graft rejection crises in renal transplant patients pretreated with donor-specific transfusions (DST) have been attributed to an antibody-mediated reaction, or an in situ primed lymphocyte test (PLT) reaction in the grafted kidney resulting from priming of recipient T cells. To test these hypotheses, we analyzed the mixed lymphocyte culture (MLC) response to donor stimulator cells in 18 DST + azathioprine (AZA)-treated patients, including 7 with living-nonrelated donors (2 HLA-haplotype mismatch) and 11 with living-related donors (1 HLA-haplotype mismatch). Studies of the kinetics of anti-donor MLC responses of PBL obtained from patients before and after DST + AZA treatment revealed shifts in the magnitude and timing of antidonor MLC response. We found an increased peak MLC response to donor and/or third-party in 6/18 patients, 4 of whom had early rejection crises; the other 2 patients had blocking factors in their post-DST plasma that strongly (57-71%) inhibited their MLC response. Plasma factors were implicated in the mechanism of early graft crisis, in that patients with an enhanced MLC response in the presence of post-DST plasma showed a significantly (P less than .02) shorter time to first rejection episodes as compared with patients with plasma blocking factors. Finally, we confirmed the findings of others that a significant proportion (7/18) of DST + AZA-treated patients had a decreased MLC response. Although such patients experienced classic (2nd week or later) rejection episodes, none had a DST-type (less than or equal to 3 day) crisis. Our data supports the concept of T cell priming by DST, and suggests that patients who fail to develop concomitant suppressor cells or humoral blocking factors will develop a rapid onset cellular rejection crisis in the transplanted kidney.

Azathioprine↗
PubMed1985

Improved renal allograft survival following donor-specific transfusions. I. Induction of antibodies that inhibit primary antidonor MLC response.

Our purpose was to identify humoral factors induced by donor-specific transfusion (DST) plus azathioprine (AZA) that correlate with improved renal allograft survival (92% at 3-34 months posttransplantation) in a group of 24 DST patients. Plasma was obtained from patients prior to AZA and DST (to), 2-6 weeks after the final transfusion but immediately prior to transplant (tt), and 6-12 weeks after renal transplantation and initiation of standard posttransplant immunosuppressive therapy (tx). Plasma was screened for inhibitory or stimulatory activity in a 6-day primary MLC, with either patient to PBL or unrelated control PBL used as responders. Patient tx plasma was uniformly inhibitory of MLC responses to donor and to pooled third-party stimulators, regardless of the source of responding cells. The tx plasma inhibition was mediated by a nondialysable factor, ruling out a direct drug effect. In contrast, the effect of tt plasma was less pronounced but more specific. In some patients, we observed a strong reproducible inhibition of antidonor MLC by tt plasma. However, other patients did not show this inhibitory effect; thus the inhibition was not statistically significant (1 greater than P greater than .05 by the Wilcoxon t test) when all patients were analyzed. Overall, patient tt plasma affected neither control antidonor MLC nor patient MLC responses to pooled allogenic stimulating cells. In two patients showing strong tt plasma inhibition of antidonor MLC, the inhibition appeared to be Ig-mediated. The results are discussed in relation to current theories of DST mechanisms.

Absorption↗
PubMed1984

Lysis of mouse macrophages, fibroblasts, and epidermal cells by epidermal alloantigen-specific cytotoxic T lymphocytes: effect of culture and inflammatory agents on Epa-1 expression.

The expression of Epa-1, a tissue-restricted non-major histocompatibility complex (MHC) alloantigen, on CBA epidermal cells (EC), fibroblasts (FB), and macrophages (M phi) was investigated using bulk-cultured and clonally-derived anti-Epa-1 cytotoxic T lymphocytes (CTL). Epa-1 was readily detected on freshly trypsinized and 24-hr-cultured EC, and on skin FB cultured for 1-3 weeks. In contrast, fresh peritoneal (PE) M phi were specifically resistant to Epa-1 CTL but became susceptible after 12-24 hr in culture. Epa-1 expression by PE M phi also could be induced in vivo by M phi-activating agents such as concanavalin A or Bacillus Calmette-Guérin (BCG), but not by the sterile inflammatory agents peptone broth or thioglycolate, suggesting a correlation between Epa-1 phenotype and M phi activation. From this and from parallel studies of spleen cell M phi it is concluded that Epa-1 may be a strain-specific marker for activated M phi in the mouse, as well as an inducible histocompatibility antigen in vivo.

Animals↗
PubMed1984

Expression of cell-defined H-Y antigen on mouse epidermal cells.

Cytotoxic T lymphocytes (CTL)5 of female origin that readily lysed syngeneic male lymphoid cells in specific, dose-dependent, H-2 restricted fashion had little or no activity against syngeneic male epidermal cells (EC) in short-term or long-term chromium-release assays. Moreover, although male EC were quite capable of priming syngeneic female lymphocytes in vivo for the accelerated rejection of male-specific skin grafts and for the subsequent generation of H-Y-specific CTL by exposure of primed female spleen cells (SC) to irradiated, syngeneic male SC in vitro, male EC themselves were incapable of stimulating the development of H-Y CTL when cocultured with primed female SC. Tests of EC from reciprocal male-female radiation chimeras revealed that keratinocytes, not marrow-derived EC (Langerhans cells), were responsible for the priming ability of EC in vivo. Moreover, H-Y antigen was serologically defined on EC that failed to express H-Y-specific CTL target-cell determinants. Alternative explanations of these findings are discussed, including the possibility that the inability of H-2-restricted T cells to lyse male EC results from the lack of association of H-Y antigen and H-2 restricting elements on the EC membrane.

Animals↗
PubMed1984

Donor-specific transfusions in unrelated and related HLA-mismatched donor-recipient combinations.

The donor-specific transfusion protocol (DST) with (DST+I) or without Imuran has resulted in improved graft survival in one-haplotype-mismatched high-MLC-reactive donor-recipient combinations. In this study we have extended the use of donor-specific transfusions to unrelated individuals (group 1), distant relatives (group 2), and two-haplotype-mismatched siblings (group 3). All grafts in group 1 and group 2 are functioning. In group 3, one patient was lost from a myocardial infarct and one kidney was lost due to rejection. In vitro testing was performed using cryopreserved cells obtained prior to transfusion (t0), after the third transfusion (tt), and after transplantation (tx). We observed patient-specific suppression in tt plasma and nonspecific suppression by tx plasma. We also found ADCC-like activity in tx, but not in t0 or tt plasma in 2 out of 3 patients. The suppressor effect of tt plasma is mediated by IgG antibody and possibly reflects an antiidiotypic antibody.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1982

Cell-mediated cytotoxicity to non-MHC alloantigens on mouse epidermal cells. VI. Influence of the MHC on the tissue specificity of cytotoxic T-lymphocyte responses.

Mice of the C3H/He and A non-H-2 backgrounds are disparate from mice of the B10 background for the tissue-restricted, non-H-2 alloantigen of epidermal cells (EC), Epa-1, that is expressed by EC but not by lymphocytes (LC), as well as for a number of other alloantigens of the B10 background that are expressed by both EC and LC, generically referred to as "lymphocyte/epidermal alloantigens" (LEA). In this study, we compared the ability of various H-2 congenic strains on the C3H or A backgrounds to mount cytotoxic T-lymphocyte (CTL) responses to EC from H-2 compatible mice of the B10 background. High responses to Epa-1 were detected only in the H-2a and H-2k haplotypes; H-2b, H-2o1, H-2s, H-2t1, and H-2t2 haplotypes were nonresponders to Epa-1. High responses to LEA were detected in H-2a, H-2b, H-2s, H-2t1, and H-2t2 haplotypes; H-2k and H-2o1 were nonresponsive to LEA. Analysis of the H-2K, I and D region alleles of responders indicates that H-2Kk is essential for anti-Epa CTL responses, whereas Dd, Db or Ks were all permissive for strong anti-LEA responses. The ability to mount a given CTL response was not associated with differences in I-region alleles. These results are discussed in terms of K/D region products serving as Ir-gene products for CTL and in determining the apparent tissue-specificity of CTL.

Animals↗