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At least 19 recordsLinked to original sources

PubMed1995

Elevated inflammatory cytokine levels in bone marrow graft rejection.

Graft rejection and graft failure represent major obstacles in allogeneic bone marrow transplantation (BMT). Cytokines possibly play a central role in the inflammatory and allospecific components of allograft rejection. Therefore, we evaluated inflammatory cytokine levels following BMT in 12 consecutive patients with graft rejection (GR). Seven of the patients underwent BMT from siblings (6 matched and 1 mismatched), 4 patients received bone marrow from other family members (3 mismatched and 1 matched), and 1 patient underwent HLA-matched unrelated BMT. Nine of 12 had a sex-mismatched BMT and 5/12 had an ABO-mismatched BMT. Nine of 12 underwent T cell-depleted (Campath anti-CDw52 moAb) BMT. Rejection was defined as marrow hypoplasia with a peripheral white blood cell count < 0.5 x 10(9)/L 21 days after BMT, in conjunction with the absence of donor cells by polymerase chain reaction analysis using a sex-mismatched probe and/or a tumor-specific probe (BCR/ABL). Twenty-five patients who underwent uneventful BMT with no GR served as controls. The levels of tumor necrosis factor (TNF), interleukin-6 (IL-6), and interleukin-1 (IL-1) were evaluated by a high sensitive RIA or an enzyme immunoassay. The levels of TNF and IL-6 were found to be higher in 10/12 and 7/7 evaluated GR patients, respectively, as compared with controls (P < 0.05). The level of IL-1 was high only in 2/12 patients. TNF elevation occurred in all patients immediately after GR. TNF and IL-6 levels were significantly higher for patients with early rejection (< 35 days after BMT) as compared with patients with late rejection (> 35 days after BMT) (P < 0.049 and P < 0.006, respectively). Eight patients engrafted after the second transplant (2 only transient). All 6 patients with stable engraftment are alive (4 with basic disease), while the 4 patients who did not engraft and the 2 patients with only transient engraftment died. In the 6 patients with no engraftment or only transient engraftment, the elevated TNF levels remained high; in the 6 patients who had stable engraftment after retransplant, TNF levels, but not IL-6 levels, decreased. In conclusion, a majority of the patients with GR displayed high levels of inflammatory cytokines (TNF and IL-6). Dysregulation of inflammatory cytokines may be involved in the pathogenesis of GR.

ABO Blood-Group System↗

PubMed1978

Analysis of the major histocompatibility complex in Syrian hamsters. I. Skin graft rejection, graft-versus-host reactions, mixed lymphocyte reactions, and immune response genes in inbred strains.

Five inbred strains of Syrian hamsters (Mesocricetus auratus) were examined for the presence of disparity at a genetic region similar to the major histocompatibility complex in other species. Vigorous reciprocal alloreactions developed in several strain combinations, which resulted in acute skin graft rejection, strong mixed lymphocyte reactions, and potent graft-versus-host reactions. In addition, we found evidence for an immune response gene which controls the antibody response to bovine serum albumin. Patterns of alloreactivity observed for skin graft rejection, graft-versus-host reactivity, and mixed lymphocyte reactivity are compatible with the hypothesis that hamsters possess a major histocompatibility complex, but the absence of discernable disparity at a serologically defined locus makes a definitive statement premature.

Animals↗

PubMed1990

T-cell depletion for bone marrow transplantation: effects on graft rejection, graft-versus-host disease, graft-versus-leukemia, and survival.

T-cell depletion of the donor bone marrow offers the most effective approach yet reported to prevent graft-versus-host disease and its associated mortality. This approach has allowed histoincompatible bone marrow transplants for children with immunodeficiency states. It has been more difficult to apply T-cell depletion to bone marrow transplants for leukemia. Failure of engraftment and leukemia relapse are more frequent than with transplants of unmodified bone marrow. Hopefully more effective immunosuppressive and antileukemic preparative regimens can be developed to allow successful application of T-cell-depleted transplants and effective prevention of graft-versus-host disease.

Bone Marrow Cells↗

PubMed1986

Graft rejection and graft-versus-host disease: mirror images.

Graft rejection and graft-versus-host disease (GvHD) complicate bone marrow transplantation in animals and man. The likelihood of each correlates with the degree of genetic disparity between donor and recipient. However, instead of a direct relation between graft rejection and GvHD, these events are inversely correlated: in most instances, they are mutually exclusive. A similar, complex relation exists with a third possible event, graft-versus-leukaemia. Attempts to suppress graft rejection or GvHD are likely to increase the reciprocal outcomes unless additional measures are instituted.

Animals↗

PubMed1998

Mouse parvovirus infection potentiates allogeneic skin graft rejection and induces syngeneic graft rejection.

BACKGROUND: The recently identified autonomous mouse parvovirus designated mouse parvovirus-1 (MPV-1) persists in adult BALB/c mice for at least 9 weeks, infects lymphoid tissues, interferes with the ability of cloned T cells to proliferate, and exhibits immunomodulatory properties. As a consequence of these findings, the present studies were undertaken to characterize further the inmunomodulatory effects of MPV-1 on T cell-mediated immune responses in vivo and in vitro. METHODS: To evaluate the effect of MPV-1 infection on CD8+ T cell-mediated responses, BALB/c-H2dm2 mice were infected after transplantation of allogeneic BALB/c skin. RESULTS: MPV-1 potentiated the rejection of allogeneic skin grafts. This potentiation was not a result of virus infecting the cellular or vascular component of the graft as determined by in situ hybridization, but was mediated by T cells. However, the proliferative capacity of alloantigen-reactive lymphocytes from graft-sensitized infected mice was diminished. MPV-1 also induced the rejection of syngeneic skin grafts, and T cells from these infected graft-sensitized mice lysed syngeneic P815 target cells. CONCLUSIONS: These results suggest that MPV-1 infection of skin-grafted mice may disrupt normal mechanisms of peripheral tolerance and provide a unique model to study virus-induced autoimmunity.

Animals↗

PubMed1984

[Immune reactions after allogeneic small bowel transplantation. Graft rejection and graft versus host reaction in the rat model].

Small bowel transplantation is characterized by the specific immunological problem of graft versus host reaction (GVHR) which appears in addition to rejection reaction. GVHR is induced and maintained by the immunocompetent cells of the graft. In order to clarify the basic mechanisms of these interfering reactions heterotopic accessory small bowel transplantations in the rat were carried out. Immunological reactions were estimated by assessment of mortality rates of recipients, histological examinations, and measurement of cytotoxic T-cell reactivity within the graft and recipient. The strength of the rejection reaction depends on the degree of histoincompatibility between donor and recipient, and the length of the graft. The expression of GVHR is also dependent on the histoincompatibility of the donor and the amount of lymphatic tissue grafted within the small intestine. The GVHR shows a characteristic time course, peaking 20 days after transplantation. GVH-T-cell-reactivity can be found in different lymphatic compartments of the graft and recipient. GVHR causes autoimmune reactivity within the recipients. These results clarify basic immunological mechanisms of rejection and GVHR thus providing an indispensable condition for clinical small bowel transplantation.

Animals↗

PubMed1990

Animals bearing malignant grafts reject normal grafts that express through gene transfer the same antigen.

Breaking the state of immunological unresponsiveness of tumor-bearing individuals to cancer is a prerequisite for active or passive tumor-specific immunotherapy. To study this problem the immunogenic MHC class I antigen, K216 was transfected into a progressor tumor. The transfected tumors were regularly rejected by normal mice but grew progressively in mice bearing nontransfected tumors. In addition, transgenic mice were derived to obtain normal cells and tissues expressing the same K216 gene product. Normal mice rejected K216-positive normal or malignant tissue grafts and generated K216-specific CTL in vitro and in vivo in response to these challenges. In contrast, mice bearing nontransfected tumors, though rejecting K216-positive nonmalignant tissue grafts, did not reject K216-positive tumors nor generate K216-specific CTL in response to K216-positive tumor cells. Mice bearing K216-positive tumors also rejected the nonmalignant K216-positive tissue grafts, but this in vivo response failed to lead to rejection of the simultaneously present tumor graft expressing the same antigen; in fact, immunity had no measurable effect whatsoever on tumor size or incidence and caused no selection for antigen loss variants. Taken together, the present findings suggest that transfer of expression of a target antigen into nonmalignant cells provides a way for obtaining effective stimulation of antigen-specific CTL in tumor-bearing mice, but that additional manipulations will be required to cause immunological rejection of established tumors.

Animals↗

PubMed1989

Third-party-mediated graft rejection and graft-versus-host disease after T-cell-depleted bone marrow transplantation, as demonstrated by hypervariable DNA probes and HLA-DR polymorphism.

Graft rejection after marrow transplantation is generally thought to be mediated by alloreactive immune effector cells of host origin. Transfused blood products also contain immune cells capable of alloreactivity against both donor graft and host. To reduce the risk of transfusion-associated graft-versus-host disease (GVHD) and graft rejection, standard procedure is to irradiate all blood products with at least 1,500 rad before transfusion. We report a patient with chronic myelogenous leukemia who developed graft rejection and GVHD after receiving a T-cell-depleted transplant from a serologically HLA-A, B, DR/DQ matched and mixed lymphocyte culture (MLC) nonreactive unrelated donor. Cytogenetic analysis of marrow cells collected at the time of graft rejection revealed a PH1-negative female karyotype that was not consistent with donor cells. Use of specific minisatellite DNA probes (YNH 24, H-RAS, and 3' HVR) revealed the exclusive presence of third-party (neither donor nor recipient) restriction-fragment-length polymorphisms (RFLP) in both peripheral blood and marrow. Repeat RFLP analysis 3 days later showed persistence of this unique third-party banding pattern. DNA-based HLA-typing, using polymerase chain reaction (PCR) and oligonucleotide probe hybridization, also showed these cells to be derived from an individual whose HLA-DR type was distinct from donor and recipient. Together, these findings suggested the presence of a proliferating population of transfused cells possessing alloreactivity against both donor graft and host, despite prior irradiation of all blood products with 2,000 rad. Limiting dilution analysis to assess the frequency of irradiated lymphocytes able to respond to mitogen revealed an approximate 5- to 6-log reduction at 1,500 to 2,000 rad as compared with unirradiated controls. These data indicate that a small percentage of lymphocytes can survive irradiation at these doses and suggest that existing blood-product irradiation guidelines may require reassessment, especially in T-cell-depleted transplant recipients.

Bone Marrow Transplantation↗

PubMed1989

A novel cell type responsible for marrow graft rejection in mice. T cells with NK phenotype cause acute rejection of marrow grafts.

Acute rejection of allogeneic and semiallogeneic marrow grafts has long been considered to be a function of the natural immune system because it shares many features with NK activity in mice. With the use of a recently developed in vivo adoptive transfer assay in which spleen cells are transferred from mice able to reject a particular marrow graft into mice that fail to do so, we show that the cells responsible for induction of marrow graft rejection indeed display the phenotype of NK cells: they lack the T cell Ag CD4 and CD8 but express the NK Ag NK1 and ASGM1. The rejection induced by adoptively transferred cells is exquisitely specific--a feature that points to a specific recognition process by the transferred cells. To elucidate what the recognition structure on these cells may be we found that they express CD3 and most likely the beta-chain of the TCR. Highly purified responder cells with the NK1+, CD3+, CD4-, CD8- phenotype, when transferred into nonresponder recipients, cause specific marrow graft rejection. We conclude that the acute rejection of bone marrow grafts is caused by a cell that expresses NK phenotype but is of T cell lineage. This may suggest the specificity of acute marrow graft rejection is caused by a specific recognition process that involves TCR.

Animals↗

PubMed1983

Clonal analysis of the lymphoid cells mediating skin allograft rejection. Mediation of graft rejection in vivo by cloned Lyt-1+2- proliferative, noncytotoxic long-term cell lines.

Studies were undertaken to elucidate the cellular basis of skin allograft rejection mediated by long-term cultured cell lines and clones. The adoptive transfer, in vivo, of in-vitro-sensitized cells, from B6AF1 anti B10.BR or from C57BL/6 anti DBA/2 cultures, and expanded eight-fold to ten-fold for one week in lectin-free interleukin 2 (LF-IL-2) were able to mediate specific skin allograft rejection. These same cells lost the ability to mediate accelerated skin graft rejection when they were expanded more than 100-fold during three weeks of culture in LF-IL-2 even though these cultures mediated high levels of specific in vitro cytotoxicity for the appropriate allosensitizing cells. When Lyt-2+ cells were depleted using monoclonal antibodies and complement prior to in vitro sensitization and expansion in LF-IL-2, these cells lines retained the ability to mediate skin allograft rejection in vivo when expanded more than 100-fold for three culture generations in vitro. These latter lines were greatly enriched for Lyt-1+2- cells and had little or no cytolytic activity, but they retained specific in vitro proliferative responses to the sensitizing alloantigen. Several Lyt-1-2+ cloned long-term lymphoid cell lines with high levels of specific cytolytic activity against the sensitizing alloantigen were derived and none was capable of mediating the accelerated rejection of skin grafts in vivo. However, cloned lymphoid cell lines that were phenotypically Lyt-1+2- and were capable of proliferating when in contact with specific alloantigen, but were not cytolytic, were capable of mediating the accelerated rejection of skin grafts in vivo both in irradiated mice and in nude mice. These studies demonstrate that skin allograft rejection can be mediated by Lyt-1+2- cell lines with specific in vitro proliferative activity to alloantigen although Lyt-1-2+ cell lines with cytolytic but not proliferative activity to alloantigen in vitro are ineffective in mediating graft rejection in vivo. Specific proliferative activity and no cytolysis appears to be a good in vitro correlate of the in vivo activity of long-term cultured cell lines.

Animals↗

PubMed1982

Cells mediating graft rejection in the mouse. III. Ly-1+ precursor T cells generate skin graft rejection.

Skin graft rejection in ATXBM CBA mice reconstituted with naive (nonsensitized) cells was shown to be mediated predominantly by Ly-1+2- effector T cells. Thus, after the treatment of the inoculum with the monoclonal anti-Ly-1.1 antibody and complement, C57BL/6 skin grafts survived indefinitely, whereas Ly-2 antibody depletion merely delayed the onset of rejection. This showed that a Ly-1+2- precursor cell rather than a Ly-1+2+ cell was the progenitor of the Ly-1+2- graft rejection effector cell. Nevertheless, another T cell subset augmented the rejection of ski grafts and it was concluded that LY-1,2,3+ cells also provided a pool of precursor cells. Thus, it appeared that both Ly-1+ and Ly-1,2,3+ cells can function as precursor cells for the effector cells, which, as shown previously, have the ly-1+ phenotype.

Animals↗

PubMed1981

Cells mediating graft rejection in the mouse. I. Lyt-1 cells mediate skin graft rejection.

The Ly phenotype of cells mediating skin graft rejection was determined using monoclonal anti-Lyt-1.1 and Lyt-2.1 antibodies in CBA mice that received CBA lymphoid cells from mice sensitized to C57BL/6; i.e., alloantigenic differences arising from the H-2 and non-H-2 loci. It was clear that graft rejection was due wholly to the presence of Lyt-1 cells in the inoculum and that Lyt-123 or Lyt-23 cells had no effect. Furthermore, no synergism was noted between Lyt-1 and Lyt-2 cells. In this model, both the cytotoxic T cell and cytotoxic lymphocyte precursors were shown to be Lyt-123 and these could be depleted from sensitized Lyt-1 populations that mediated graft rejection. Thus cytotoxic T cells are not responsible for skin graft rejection, but rather, this is mediated by an Lyt-1 cell. Whether this T cell is distinct from other Lyt-1 cells (T helper, T cells mediating delayed hypersensitivity) is not clear at present, but other evidence, and traditional concepts, link graft rejection and delayed type hypersensitivity as being different manifestations of the same mechanism.

Animals↗

PubMed1985

Millipore diffusion chambers allow dissociation of myelin phagocytosis by non-resident cells and of allogenic nerve graft rejection.

Allogenic graft rejection leads to rapid tissue destruction of nerves transplanted directly into a muscle lodge. If the nerves are enclosed in 5.0 micron pore chambers and transplanted into the peritoneal cavity, there is no allogenic graft rejection. The phagocytosis of myelin by invading cells is, however, not disturbed, showing that these cells can distinguish the degenerating myelin from the Schwann cell without being responsive to the Schwann cell's allotype. If the allografts are allowed to predegenerate for 4 wk in 0.22 micron pore chambers which do not admit any cells, there is a striking mitigation of the allogenic graft rejection if the nerves are subsequently released from the chamber. Myelin phagocytosis in such nerves is also reduced. These observations indicate the existence of a hierarchy of cellular recognition mechanisms involved in nerve tissue degradation. Phagocytosis of the myelin sheath by macrophages involves recognition mechanisms which differ from those of the allogenic rejection of the Schwann cell, presumably mediated by T lymphocytes.

Animals↗

PubMed1994

Acute kidney graft rejection. A morphological and immunohistological study on "zero-hour" and follow-up biopsies with special emphasis on cellular infiltrates and adhesion molecules.

Serial biopsies from 41 consecutive renal allotransplanted patients were evaluated in order to obtain pretransplant data as well as information on well-functioning and acutely rejecting grafts. Each patient served as his own control. Thirty-five patients were followed according to the schedule which included biopsy prior to transplantation, shortly after opening of reanastomosis, at least once postoperatively (days 7-10), and furthermore whenever clinically indicated. The morphological evaluation was in each case combined with immunofluorescence (to detect immunoglobulins and complement fractions) and immunohistochemistry with a wide panel of monoclonal antibodies for T cells (CD2, CD3, CD4, CD8, gamma delta), B cells (CD20, CD22), macrophages (CD68, MAC387) NK cells (leu-7, CD16), activation markers (IL-2-R, Ki-67, transferrin-R), MHC antigens (HLA-ABC, HLA-DR), adhesion molecules (ICAM-1, VCAM-1, ELAM-1, PADGEM, VLA-4, LFA-1 alpha/beta), and growth factors (EGF, TGF-alpha, EGF-R). When 132 biopsies and 10 failed allografts were examined, no specific morphological or immunohistological parameter predictive of rejection or graft outcome could be found. Morphology in follow-up biopsies from non-rejecting and rejecting patients revealed a continuum of inflammatory changes, and several non-rejecting cases demonstrated cellular inflammatory infiltrates which could not be discriminated from those seen in acute rejection. Of the patients 44% had acute rejection accompanied by increased infiltration of T cells and macrophages showing enhanced IL-2-R expression, increased tubular and endothelial staining for MHC class II, ICAM-1, and VCAM-1, and strong leukocytic expression of VLA-4 and LFA-1 alpha/beta.

Adolescent↗

PubMed1984

Excretion of urokallikrein in renal transplant patients. Relation to graft rejection, renal function, and blood pressure.

The relation between urinary kallikrein excretion ( Ukal ) and rejection, graft function, and blood pressure was studied in 45 renal transplant recipients. Ukal was assayed by means of an enzymatic (amidolytic) method, as well as with a specific radioimmunoassay. In a group of 10 patients studied longitudinally from the day of transplantation till day 35 +/- 3, an increase in urinary amidolytic activity without a concomitant increase in kallikrein antigen excretion was found to precede 11 out of 14 rejection episodes. This increased amidolytic activity generally persisted for several days. It was demonstrated by chromatography using an immunoadsorbent column of antiurokallikrein that the rejection-associated esterase, or esterases, differed from urokallikrein . In 35 outpatient recipients with stable graft function, Ukal excretion was decreased compared with that of healthy controls (42 +/- 7.5 vs. 107.5 +/- 7.3 micrograms/24 hr by radioimmunoassay and 0.70 +/- 0.08 vs. 1.10 +/- 0.07 U/24 hr, using the amidolytic method); for these patients a significant correlation between Ukal excretion and creatinine clearance was found (P less than 0.02). Both in transplant recipients and in controls there was a close correlation between the results of the two Ukal assays (P less than 0.001). No significant relation between Ukal excretion and blood pressure was found, either for patients or for controls. It is concluded that acute graft rejection is accompanied by an increased excretion of nonurokallikrein esterase(s). The lower Ukal excretion in patients with stable renal function seems to be related to their reduced renal function. No relation between Ukal excretion and blood pressure levels was found.

Adolescent↗

PubMed1982

Graft rejection in sponges. Genetic structure of accepting and rejecting populations.

Graft rejection frequencies in a population of the sponge Ectyoplasia ferox are reported in relation to the complexity of the histocompatibility system in this species. The frequency of graft acceptance is high but we show that, despite assumptions in the literature to the contrary, this does not imply that sponges accepting each other's grafts are genetically identical. This paper reports that graft-accepting pairs of sponges can have dissimilar plasmalemmal proteins. In addition, a theoretical analysis is presented of the types of histocompatibility systems that would account for the present results and those of others. We concluded that there is no evidence that sponges have highly polymorphic histocompatibility systems. The paper also reports on the histology of graft rejection and discusses some of the ecological relevance of the findings.

Alleles↗

PubMed1991

Immunological aspects of corneal graft rejection.

Immunological graft rejection is a major cause of corneal graft failure. HLA class I and II antigens are expressed by various cells within the cornea and during sensitisation of the recipient donor antigens appear to be presented by both donor and recipient antigen presenting cells. Certain donor and host factors have been shown to influence the incidence of corneal graft rejection, and the manipulation of these factors is discussed.

Corneal Transplantation↗

PubMed1997

Pancreatitis-associated protein: a putative marker for pancreas graft rejection.

BACKGROUND: Graft rejection is one of the major causes of graft loss after pancreas transplantation. Pancreatitis-associated protein (PAP) is synthesized by the pancreas due to pancreatic inflammation and has shown to be a good serum marker for injury of the pancreas. It may also be potentially useful in the early recognition of rejection and may thus improve pancreas survival. METHODS: We retrospectively evaluated PAP as an early serum marker of pancreas graft rejection in a cross-sectional study in which immunohistochemical analysis of pancreas biopsies was undertaken using antibodies against PAP. PAP concentrations were also measured in sera of blood donors and in patients with renal failure, renal replacement therapy, kidney transplantation alone, and simultaneous pancreas-kidney transplantation. RESULTS: All patients had elevated PAP serum levels compared with blood donors (median PAP: 22 ng/ml, range: 5-75 ng/ml; P<0.0001). Patients on renal replacement therapy had higher values than patients with renal failure (median: 420 ng/ml and 150 ng/ml, respectively). There was a strong inverse correlation between PAP levels and creatinine clearance (P<0.001). PAP values in simultaneous pancreas-kidney transplantation patients with histological rejection were significantly higher than values in those who were clinically stable (median: 925 ng/ml and 322 ng/ml, respectively; P=0.006). Rejection was significantly associated with PAP staining of acinar cell surface. There was also a significant correlation between surface positivity of staining and serum PAP levels (P=0.008). No positive PAP staining was observed in concurrently collected biopsies of renal allografts undergoing rejection. CONCLUSIONS: Serum PAP levels appear to strongly correlate with creatinine clearance measurements. In patients with a pancreas-kidney transplantation, PAP may prove to be a useful biological and histological marker of pancreatic graft rejection.

Acute-Phase Proteins↗