ISSN:0041-1337    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

Using congenic strains of rats, the effect on the rejection of small bowel transplants across isolated major histocompatibility compelx (MHC) and nonMHC antigenic disaprities was examined. The medial survival time of small bowel grafts across MHC differences in the LEW anti-LEW. 1N and LEW. 1N anti-LEW strain combinations was 14 and 12 days, respectively. The median survival time across the nonMHC antigenic difference in the BN anti-DA.1N strain combination was 20 days, which was significantly longer than the rejection time across the MHC differences (P>0.005). Both hemagglutinating and cytotoxic antibodies were produced in all three strain cominations, but the magnitude of the response varied considerably and did not correlate with the time of rejection. In the case of MHC differences, the antibody was directed against both class I and class II antigens, and with the nonMHC difference, the greatest respnose was directed against the major blood group antigen RT2.

ISSN:0041-1337    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

One of the major complications of allogeneic bone marrow transplantation is graft-versus-host disease. This can be avoided by removing the mature T cells from the marrow, most conveniently by the use of monoclonal antibodies. However, T cell purging results in an increased tendency for the recipinet to reject the donor marrow. We have developed monoclonal antibodies to L3/T4 and Lyt-2 that specifically deplete functional T cell subsets in mice. We demonstrate that such reagents can be used to control both graft-versus-host disease and marrow rejection in mouse models of bone marrow transplantation across one-haplotype or two-haplotype major histocompatibility differences. Such strategies to abrogate host resistance, by administration of anti-T-cell monoclonal antibodies to the recipient, may complement marrow T cell purging for human allogeneic bone marrow transplantation.

ISSN:0041-1337    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

α-Thalassemic heterozygous (Hbath/+) mice were used to investigate the possible selective advantage of transplanted normal (+/+) hemopoietic cells. Without conditioning by total-body irradiation (TBI), infusion of large numbers of normal bone marrow cells failed to correct the thalassemic peripheral blood phenotype. Since the recipient's stem cells are normal with respect to number and differentiation capacity, it was thought that the transplanted stem cells were not able to lodge, or that they were not stimulated to proliferate. Therefore, a nonlethal dose of TBI was given to temporarily reduce endogenous stem cell numbers and hemopoiesis. TBI doses of 2 or 3 Gy followed by infusion of normal bone marrow cells proved to be effective in replacing the thalassemic red cells by normal red cells, whereas a dose of 1 Gy was ineffective. It is concluded that cure of thalassemia by bone marrow transplantation does not necesarily require eradication of thalassemic stem cells. Consequently, the objectives of conditioning regimens for bone marrow transplantation of thalassemic patients (and possibly other nonmalignant hemopoietic disorders) should be reconsidered.

ISSN:0041-1337    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

We have studied here cytotoxic function of three cloned cell lines—TC12, 48, and 50—derived from circulating lymphocytes that were potentially able to eliminate residual tumor cells in a patient transplanted for treatment of acute lymphocytic leukemia. These cloned cells, which have both phenotypic and functional characteristics of natural kiler lymphocytes, were tested in chromium release assays against a panel of 16 uncultured populations of leukemia cells. In addition, their activity was compared with that of cloned and uncloned NK cells from normal individuals.It was found that TC clones induced a much weaker degree of killing against fresh tumor cells compared with conventional NK target cell lines such as K562 or MOLT4. In addition, there was great heterogeneity in their individual lytic capacity against the various leukemia blasts (TC12, 48, and 50 cells killed in a significant fashion, respectively, 7, 1, and 4 of the 16 leukemias), reflecting the functional diversity of normal NK cell populations. Thus, for a fraction of leukemias, there was no correlation between lytic ability of TC cells and that of uncloned lymphokine-activated large granular lymphocytes from normal peripheral blood.Together, these results support the view tht direct identification of patients' cytotoxic lymphocytes screened against in vivo relevant tumro cells is necessary to evaluate potentially beneficial immunologic responses in the context of bone marrow transplantation.

ISSN:0041-1337    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

Immunoglobulin and specific antibody levels are well maintained in the recipients of T-cell-deplated allogeneic bone marrow transplants (BMT), even though up to 99% of mature T cells are removed from the donor graft. For 3–8 weeks after the procedure, natural killer (NK) cells with an activated pattern of target cell killing have been shown to circulate in the recipient. This study investigates whether these reicipient NK cells spontaneously secrete lymphokines that modulate B cell function in a way analogous to that of in-vitro-activated NK cells from nromal individuals. Large granular lymphocytes (LGLs) (which contain a high proportion of NK cells) have been prepared from the peripheral blood of 11 recipients of T-cell-depleted major-histocompatibility-complex-matched allografts. In the first 4–6 weeks after BMT these LGLs were found spontaneously to secrete interleukin 2, interferon gamma and B cell differentiation factor. While secretion of these factors declines by 20–24 weeks after BMT, the quantitities are still greater than those seen from control donors. Patinet LGLs are also able to activate autologous (donor) B cells, rendering them potnetially responsive to the secreted factors. It apears likely that activated NK cells (or LGL) play a significant role in maintaining B cell function in vivo after T-cell-depleted BMT.

ISSN:0041-1337    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

Cyclosporine levels by radioimmunoassy (RIA) and high-performance liquid chromatography (HPLC) were monitored in serial blood samples (n=177) from 11 renal allograft recipients. HPLC analysis revealed three parimary metabolities of CsA (M17, and M21) in peak and trough blood samples; M17 was the preponderant metabolite. In 4 patients on whom serial metabolite assays were performed, M17 was found in the blood at 86–2004 ng/ml; M1 and M21 were found at up to 100 ng/ml. The immunosupressive properties of purified metabolities M1, M17, M21, and M8 (which was not detected in the blood) were compared with CsA. M17—and, to a lesser extetent, M1 and M21—were found to inhibit the in vitro response of human mononuclear cells in the mixed leukocyte culture and in mitogen (phytohemagglutinin [PHA], eoncanavalin A [Con A], and pokeweed mitogen [PWM]) assays at 1000 ng/ml. M8 exhibited no in vitro inhibitory activity. M17 was further tested at 10–1000 ng/ml in PHA and mixed lymphocyte culture (MLC) assays. M17 had considerably less inhibitory activity (12–43%) than CsA (18–70%) in the PHA assay. However, in MLC experiments M17 blocked the proliferative response by 39–72% at 100–800 ng/ml, which appoached the degree of inhibition exhibited by CsA (63–87%). In 34 of 37 (92%) patient blood samples, the level of metabolite M17 was found to exceed the parent drug leve and could not be measured accurately by RIA. The observed in vitro immunosuppressive activity of metabolities (particularly M17) and their presence in the blood of renal allograft recipients suggest a possible role for thes emetabolities in the immunopharmacology of CsA.

ISSN:0041-1337    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

High levels of allosensitization (<50%), which often occur in dialysis patients awaiting renal transplant, make donor selection difficult. Such patients may be included in elabroate protocols in which they are crossmatched with all available ABO compatible donors, or crossmatching may be deferred until a very-well-matched with all available. ABO compatible donors or crossmatching may be deferred until a very-wellmateched donor becomes available. The former approach of random crossmatching is costly and inefficient, while that latter approach may overlook crossmatch-compatible donros. We believe that the identification of antibodies present in highly reactive sera and the use of this information in donor selection woul increase the frequency of crossmatch-negative donors for these patients. In this study eleven sera, reactive with 70% to 100% of a random cell panel, were obtained from multiply transfused dialysis patients. Sera were analyzed by standard (CDC) and antiglobulin augmented (AHG-CDC) lymphocytotoxicity, and by differential absorption with HLA-typed platelets. All sera contained only one or two antibodies directed against the high frequency public HLA epitopes, accounting for 85% to 100% of each serum's total reactivity. These characterized sera were crossmatched with 114 random normal donors. The frequency of negative crossmathces was 20.5%. However, if the serum antibody data had been used to preselect donors for crossmatch—that is, to exclude donors that were likely to be possitive—the negative crossmatch frequency would have increased to 86.4%. The use of the serum analysis data in donor selection would have reduced the total number of requried crossmatches by 78%. Serum analysis correctly predicted the outcome of 95.6% of crossmatches performed with an average of 3% false positives and 1.3% false negatives. This approach to donor selection reduces

ISSN:0041-1337    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

An attempt was made at correcting the specific lysosomal enzyme deficiencies in 7 children with Hunter's or Hurler's diseases by transplantation of fetal fibroblasts. In spite of pretreating the young patients with stored blood, following a procedure employed successfully to avoid rejection of kidneys from incompatible donors, the use of serum-free media for culturing the cells before being harvested and incubation of the cells with chorionic gonadotrophin, the transplantation of fetal fibroblasts was not associated with biochemical or clinical changes. None of the seven patients showed immune reactions against the transplanted cells, HLA antigens, or the missing enzymes.

ISSN:0041-1337    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

Human epidermal cells from a small skin specimen can be grown in culture into multilayered sheets suitable for the permanent coverage of large burn wounds when used as epidermal autografts. We report hare on the long-term survival of such cultured epidermal sheets used as epidermal allografts (EAG) across a major hisocomaptibility barrier in three nonimmunosuppressed adult patients, suffering from large chronic grafted leg ulcers, where the EAG have been placed to cover the conventional split-thicknes skin autograt donor site. The absence of rejection was based upon clinical, histological, and immmunopathological observation of the allografted sites at various intervals after grafting of the EAG. The identity of the epidermal cells on the grafted area with cultured cells from allogeneic donor was then established after blood substance typing by indirect immunofluorescence.Furthermore, epidermal cells from cultured sheets, but not control human cells from freshly excised normal epidermis, failed to stimulate the recipient peripheral blood cells in the mixed epidermal cell lymphocyte culture reaction, a finding that is related to the complete absence of class-II-antigen-bearing cells in cultured epidermis. This absence of T cell stimulation was noted not only on the day of grafting but throughout the follow-up. Althogether, these findigns show that Langerhans cell and other class-II-angtigen-bearing cell-deplated cultured epidermal allograts, are tolerated in unrelated recipients. EAG may serve as a skin substitute in patients with large wounds or burns. Since EAG may be grown continuously, the coverage of burns may not then be limited by the availability of the donor site, or by the time necessary to produce epidermal tissue in cultures.

ISSN:0041-1337    

出版商:OVID    

年代:1986

数据来源: OVID