PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “rejection”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 127 records · Page 7Linked to original sources
PubMed1983

Immune mechanisms in organ allograft rejection. II. T helper cells, delayed-type hypersensitivity, and rejection of renal allografts.

The cellular requirements for renal allograft rejection have been assessed by adoptive transfer studies in a rat model. Sublethally irradiated (780 rads) LEW (RT1l) recipients of WF (RT1u) renal allografts were selectively reconstituted with spleen cells from specifically sensitized donors. In some experiments the reconstituting inocula were depleted of SIg+ cells by passage over anti-Ig columns or subjected to additional depletion of cytotoxic T cells (Tc) and their precursors reactive with monoclonal antibody OX8. WF renal allografts underwent acute rejection in the unmodified LEW recipient with day 7 serum creatinines of 6.8 +/- 0.9 mg/dL (mean +/- SD; n = 7), graft histology characterized by marked mononuclear cell infiltration and evidence of a brisk humoral response (complement-dependent cytotoxicity (CDC) titer greater than 2(6] and generation of Tc demonstrable by in vitro monitoring. Sublethally irradiated recipients mounted no detectable immune response, and day 7 serum creatinine and graft histological findings were not significantly different from those obtained in isograft controls. Renal allografts were, however, rejected in sublethally irradiated recipients reconstituted with unfractionated immune spleen cells, as evidenced by functional and histologic criteria (day 7 serum creatinine of 5.5 +/- 1.2 mg/dL; histology characterized by extensive interstitial hemorrhage, fibrinoid necrosis of blood vessels, and polymorphic infiltration). Neither antibody nor Tc appear, in this model, to be required to effect rejection, because recipients reconstituted with inocula depleted of SIg+ cells (day 7 CDC titer less than 2l) or subjected to additional depletion of Tc and their precursors (day 7 lymphocyte-mediated cytotoxicity assay: % specific chromium release at 100/1 E/T ratios less than 5%) underwent acute rejection with a day 7 serum creatinine of 5.0 +/- 1 and 4.3 +/- 1.5 mg/dL, respectively, and histological findings were characterized by marked mononuclear cell infiltration and a paucity of hemorrhage.

Animals↗
PubMed1980

Analysis of the mechanism of allograft rejection and cell-mediated immunity. I. Accelerated rejection of tumour allografts without augmented cytotoxicity in the spleen cells.

While immunization with allogeneic spleen cells did not generate positive cytotoxic activity, it produced accelerated rejection of subsequent tumour grafts carrying the same H-2 antigen. No augmented generation of cytotoxicity was detectable by 51Cr-release assay in the host spleen cells, even in the presence of accelerated rejection of tumour allografts. However, augmented cytotoxicity was generated in mixed lymphocyte culture and in peritoneal lymphocytes after an intraperitoneal boost. These results indicate that while immunization with allogeneic spleen cells does not generate mature cytotoxic T lymphocytes (CTL) detectable by the present assay, it may produce premature CTL that rapidly differentiate into mature CTL after direct contact with antigen at the site of graft rejection. The inability to generate a high degree of cytotoxicity in the spleen cells may be ascribed to the early development of CTL at the rejection site. The relationship between accelerated rejection of allogeneic tumour grafts and delayed-type hypersensitivity reactions is also discussed.

Animals↗
PubMed1996

Revision of the 1990 working formulation for the classification of pulmonary allograft rejection: Lung Rejection Study Group.

In 1990, an international grading scheme for the grading of pulmonary allograft rejection was instituted. The use of this classification has resulted in a uniformity of grading which has allowed inter-institutional collaborations and communication unique in allograft monitoring. In 1995 an expanded group of international pathologists convened and revised the original proposal. This article summarizes the updated classification for pulmonary allograft rejection. In brief, acute rejection is based on perivascular and interstitial mononuclear infiltrates. Each grade of acute rejection should mention the presence of coexistent airway inflammation, the intensity of which may also be graded. Chronic rejection is divided into bronchiolitis obliterans--active or inactive--and vascular atherosclerosis--accelerated arterial or venous sclerosis.

Acute Disease↗
PubMed1998

The role of T cells in allografted tumor rejection: IFN-gamma released from T cells is essential for induction of effector macrophages in the rejection site.

Allografted Meth A tumor rejection is T cell dependent, but T cells are inactive toward the allograft; rather, the main effector cells are allograft-induced macrophages (AIM) with MHC haplotype specificity. Here, we examined the role of T cells in the induction of AIM in the rejection site. On day 4.5 after i.p. transplantation of Meth A fibrosarcoma cells to C57BL/6 (B6) mice, we obtained a kind of precursor of AIM (pro-AIM) from the transplantation site by an enrichment technique involving adherence to serum-coated dishes. The noncytotoxic pro-AIM-rich population put into a diffusion chamber became cytotoxic against Meth A cells after 2 days in the peritoneal cavity of an untreated B6 mouse. Similar activation of the chambered B6 pro-AIM-rich population occurred in IFN-gamma -/- B6 mice, whereas there was no activation when chambers containing an IFN-gamma -/- mouse-derived pro-AIM-rich population were placed in normal or IFN-gamma -/- mice, suggesting that IFN-gamma is involved in the activation. RT-PCR experiments demonstrated that among bulk infiltrates T cells were the major producer of IFN-gamma; and most of the cells in a T cell-eliminated pro-AIM population in a diffusion chamber kept for 2 days in a B6 mouse did not become AIM. Furthermore, IFN-gamma -/- B6 mice could not reject allografted Meth A tumor cells, whereas the grafts were rejected by i.p. injections of IFN-gamma into the mutant mice. These results indicate that IFN-gamma released from allograft-induced T cells is essential for both the activation of a kind of pro-AIM to AIM in the transplantation site and the rejection of an allografted tumor.

Animals↗
PubMed1995

Allo-skin graft rejection, tumor rejection and natural killer activity in mice lacking p56lck.

Mice lacking the p56lck molecule (lck -/-) have a profound block in the maturation of thymocytes and a greatly reduced number of peripheral mature T cells. To analyze further the functions of the T cells developed in lck -/- mice in vivo, we evaluated the ability of lck -/- mice to reject allo-skin grafts and methylcholanthrene (MCA)-induced syngeneic fibrosarcoma, and also examined the biological activity of lck -/- natural killer (NK) cells. Mice lacking p56lck failed to reject skin grafts from either MHC-disparate or minor-histocompatibility-different donors, even after they had been primed with donor spleen cells. They also failed to reject the MCA-induced immunogenic syngeneic fibrosarcoma, MC57X. NK activity in mice lacking p56lck was normal, and there were no differences in the NK cell activation induced by poly(I).poly(C) stimulation or interleukin-2 stimulation (lymphokine-activated killer induction) between mice lacking p56lck and their immunocompetent heterozygous littermates. NK cells lacking p56lck mediated a normal antibody-dependent cell-mediated cytotoxicity (ADCC) response. The results of this study indicate that the loss of p56lck severely impairs the effectors of the immune system which mediate the rejection of allo-skin grafts and syngeneic tumors. The normal NK activity in lck -/- mice suggests that p56lck is not required for the development and activation of NK cells.

Animals↗
PubMed2000

Completely reversed acute rejection is not a significant risk factor for the development of chronic rejection in renal allograft recipients.

Although acute rejection (AR) has been shown to correlate with decreased long-term renal allograft survival, we have noted AR in recipients who subsequently had stable function for more than 5 years. We reviewed 109 renal graft recipients with a minimum of 1 year graft survival and follow-up of 5-8 years. Post-transplant sodium iothalamate clearances (IoCI) measured at 3 months and yearly thereafter were used to separate recipients into 2 groups. In 61 patients (stable group), there was no significant decrease ( > 20 % reduction in IoCl over 2 consecutive years) in IoCl. Forty-eight patients had significant declines in IoCl (decline group). Groups were compared for incidence, severity, timing, and completeness of reversal of AR. Rejection was considered completely reversed if the post-AR serum creatinine (Scr) returned to or below the pre-AR nadir Scr after anti-rejection therapy. The incidence of AR was not significantly different between groups (47% vs 52%). A trend toward a lower mean number of AR episodes per patient was noted in the stable group (0.69 vs 1.04, P = 0.096), but the timing of AR was not different. Steroid-resistant AR occurred in approximately 25 % of both groups. A striking difference was seen in complete reversal of AR, with the stable group having 100% (42/42 episodes of AR in 29 patients) complete reversal whereas only 32 % (8/25) of the patients in the decline group had complete reversal (P < < 0.001). Of 8 declining patients with complete reversal, graft loss was due to chronic rejection (CR) in only 3. Seventeen declining patients had incomplete reversal of AR, and 82 % (14/17) lost their grafts to CR. Overall, only 8% (3/37) of the recipients with complete reversal of AR developed CR. No patients with incompletely reversed AR had stable long-term function as measured by IoCl. AR is not invariably deleterious to long-term renal graft function if each episode of AR can be completely reversed.

Acute Disease↗
PubMed2006

Impact of repetitive episodes of antibody-mediated or cellular rejection on cardiovascular mortality in cardiac transplant recipients: defining rejection patterns.

BACKGROUND: In our previously published work dealing with antibody-mediated (vascular) rejection (AMR), we defined patterns of rejection (AMR and cellular rejection [CR]) based on a review of biopsy diagnoses taken in the first 6 to 12 weeks post-transplant. We have shown the significance of these pattern designations in relation to patient and allograft outcome in five outcome analyses. The current retrospective analysis was done to determine whether our previous criteria for pattern designations provided the greatest degree of discrimination between AMR and CR. METHODS: Six hundred sixty-five patients from the U.T.A.H. Cardiac Transplant Program were included in our study. Patients induced with OKT3 immunosuppression were excluded. We analyzed the relationship of a number of either AMR or CR episodes to cardiovascular mortality. We constructed Kaplan-Meier survival curves to assess the impact of incremental numbers of AMR or CR episodes on cardiovascular mortality. RESULTS: Three or more episodes of AMR resulted in a statistically significant increase in cardiovascular mortality. By contrast, CR episodes did not increase the risk of cardiovascular mortality. CONCLUSIONS: Based on our findings, we believe that clinical trials should be designed to test treatments based on predominant rejection patterns and that end-points for trials should be defined by number of biopsies positive for either CR or AMR. This approach may lead to improved patient and allograft survival.

Adult↗
PubMed2000

The role of the graft endothelium in transplant rejection: evidence that endothelial activation may serve as a clinical marker for the development of chronic rejection.

In this review, we discuss the role of the allograft endothelium in the recruitment and activation of leukocytes during acute and chronic rejection. We discuss associations among endothelial activation responses, the expression of adhesion molecules, chemokines and chemokine receptors, and rejection; and we propose that endothelial vascular cellular adhesion molecule-1 (VCAM-1) may be used as a surrogate marker of acute rejection and allograft vasculopathy. In addition, we describe potential mechanistic interpretations of persistent endothelial cell (EC) expression of major histocompatibility complex (MHC) class II molecules in allorecognition. The graft endothelium may provide an antigen-specific signal to transmigrating, previously activated, T cells and may induce B7 expression on locally transmigrating leukocytes to promote costimulation. Taken together, these functions of the EC provide it with a potent regulatory role in rejection and in the maintenance of T-cell activation via the direct and/or the indirect pathways of allorecognition.

Biomarkers↗
PubMed1992

Mechanism of the rejection of major histocompatibility complex class I-disparate murine skin grafts: rejection can be mediated by CD4+ cells activated by allo-class I + II antigen in CD8+ cell-depleted hosts.

In the preceding article, we analyzed the immunohistochemical rejection mechanism of major histocompatibility complex (MHC) class I (H-2K)-disparate murine skin grafts, and showed that only CD8+ cells infiltrated at the site of the epithelial tissue of MHC class I-disparate graft. We also showed that perfect survival of MHC class I-disparate grafts were attained in thymectomized recipients treated with anti-Lyt-2 monoclonal antibody. In this report, we showed that these long-surviving allo-class I grafts were rejected in the absence of CD8+ cells by stimulation with allo-MHC class I + II-disparate graft as the second stimulation. Furthermore, it was immunohistochemically revealed that under that condition, a large number of CD4+ cells infiltrated into the epithelial tissue of these long-surviving class I grafts, which were going to be rejected 2-5 d after the transplantation of a second graft with MHC class I + II difference. This result directly shows that CD4+ cells are able to became effectors for the rejection of allo-MHC class I (H-2K) skin graft.

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↗
PubMed1996

The impact of acute rejection on the development of intimal hyperplasia associated with chronic rejection.

The rat aortic model of chronic rejection was used to study the effect of acute rejection on the development of intimal hyperplasia (IH). Two model systems were studied. In the first, continuous monotherapy with mycophenolate mofetil (MM) (40 mg/dx14 d followed by 30 mg/kg/d) was initiated 2 or 4 weeks posttransplant. Digital computer image analysis was used to quantify IH. While the development of IH was delayed, it was not prevented. In allografts where MM treatment was delayed for 2 wk, a 35.5% reduction in the amount of IH was observed. Delaying drug treatment for 4 wk resulted in a 42.2% reduction of IH. In contrast, continuous therapy from the time of transplant resulted in a 76.3% reduction in the amount of IH in comparison with untreated allograft controls. To further define the role of acute rejection in the development of IH, aortic allografts, ACI or (ACIxLewis)F1 (F1), were orthotopically transplanted to Lewis recipients and then retransplanted to donor strain secondary recipients after 2 or 4 wk. Grafts were harvested at 12 weeks posttransplant. When the retransplant was performed at 2 wk, intimal hyperplasia was decreased by 55.9% in ACI and by 66.7% in F1 allografts in comparison to conventional (ACI-->Lewis) allograft controls. When retransplantation was delayed until 4 wk, IH was not decreased in ACI allografts (105.9%) and was only marginally decreased in F1 allografts (26.2%). Syngeneic control F1 grafts (F1-->F1-->F1) did not develop significant IH at 12 or 20 wk when retransplanted at 2 wk (10% and 12%, respectively) or when retransplanted at 4 wk and harvested at 12 wk (18.6%). A common feature of IH is the development of medial acellularity. Unlike conventional allograft recipients (ACI-->Lewis; no retransplantation), F1 retransplanted grafts did not develop significant medial myocyte dropout. In contrast, delayed MM immunosuppressive therapy or retransplantation of ACI allografts at 4 weeks to ACI secondary recipients resulted in significant loss of medial myocytes. Our results show that acute rejection, which occurs during the first 4 wk posttransplant, is sufficient to mediate the development of IH associated with CR. However the lack of a continued allogenic environment slows the process.

Acute Disease↗
PubMed1985

Lung allograft rejection in the rat. V. Inhaled stimuli aggravate the rejection response.

Responses to inhaled stimuli in lung allografts might intensify the rejection response against the grafts. Therefore, we investigated the rejection of lung allografts in rats exposed to various degrees of stimuli via the airways. A group of these rats was selectively decontaminated to eliminate infection of the graft. Stimuli provided were intrabronchially injected purified protein derivative in sensitized rats and dust inhaled from sawdust used as bedding in the cages. Both intrabronchially injected purified protein derivative and stimuli inhaled from sawdust were found to aggravate lung allograft rejection, thus shortening mean graft survival from 32 to 11 days. Selective decontamination did prolong lung graft survival (p less than 0.05) because it lowered the overall immune reactivity of the recipient rats. For clinical lung transplantation, these observations suggest that patients should be selectively decontaminated and protected against inhalation of exogenous stimuli during a rejection episode.

Adjuvants, Immunologic↗
PubMed1985

Immune mechanisms in organ allograft rejection. V. Pivotal role of the cytotoxic-suppressor T cell subset in the rejection of heart grafts bearing isolated class I disparities in the inbred rat.

The cellular requirements for rejection of heart grafts bearing isolated major histocompatibility complex (MHC) subregion RT1A-encoded class I disparities was assessed by adoptive transfer. Sublethally irradiated (780 rads) (PVG X WF)F1 recipients of irradiated PVG-RT1r1 heart grafts were selectively reconstituted with spleen cells from syngeneic donors previously sensitized with two sequential PVG-RT1r1 skin grafts. PVG-RT1r1 heart grafts were rejected acutely in recipients reconstituted with 10 X 10(6) unfractionated immune spleen cells (7-9 days, n = 6) or inocula (5 X 10(6) cells) depleted of SIg+ cells (10-13 days, n = 5), but additional depletion of cytotoxic T cells and their precursors (OX8+) resulted in marked prolongation of graft survival (n = 4, 4 X 10(6) cells, 45-67 days). Reducing the reconstituting inocula from 4 X 10(6) to 2.5 X 10(6) spleen cells (OX8-, SIg-) prolonged graft survival to that observed in unreconstituted recipients (generally greater than 100 days). Additional studies were performed to define the immunologic basis for prolonged survival of PVG-RT1r1 heart grafts in homozygous PVG recipients. Although lymphoid cells of naive PVG failed to proliferate (stimulation index [SI] 1.01, P = NS) on coculture with irradiated PVG-RT1r1, bulk cultures yielding but weak and variable CTL generation, lymphoid cells from specifically sensitized PVG proliferated (SI 4.25, P less than .001) and generated greater cytotoxic T lymphocyte (CTL) activity (P less than .001) under identical conditions, strongly suggesting, therefore, that prolonged heart graft survival in this strain combination is related to low CTL precursor frequency. Further, though PVG-RT1r1 heart grafts were rejected in 10-12 days (n = 3) by (PVG X WF)F1 recipients, (PVG-RT1r1 X WF)F1----(PVG X WF)F1 heart grafts (RT1Aa disparity) survived greater than 100 days despite an equivalent alloimmune response, and this was shown to correlate with a reduced sensitivity of (PVG-RT1r1 X WF)F1 target cells to lysis by CTL. These data, therefore, strongly suggest that the pivotal role of CTL in the rejection of class-I-disparate heart grafts is, in fact, related to their function in direct cell-mediated cytolysis.

Animals↗
PubMed1983

Immune mechanisms in organ allograft rejection. III. Cellular and humoral immunity in rejection of organ allografts transplanted across MHC subregion disparity RT1.B (RT1.D).

The role of T and B lymphocytes in rejection of cardiac allografts bearing isolated major histocompatibility complex (MHC) subregion RT1.B/D encoded class II "Ia" disparities was investigated using natural and congenic recombinant inbred rats (RP, PVG RT1r1). RT1.B/D-disparate heart grafts were shown in 3 strain combinations (RP leads to WF, WF leads to [RP x PVG RT1l] F1, and PVG RT1r1 leads to PVG RT1 alpha) to induce a brisk humoral response (complement-dependent cytotoxicity [CDC] titers greater than 2(6] with specificity for class II determinants as evidenced by strain and tissue distribution of susceptible targets. Cytotoxic T cells (Tc) generated in parallel effected equivalent lysis (in the 4-hr 51Cr-release LMC assay) of con A and lipopolysaccharide (LPS) blasts of the same strains. Specificity of Tc for class II determinants was demonstrable by specific inhibition of killing (congruent to 50%) by anti-Ia antibody preparations (monoclonal 0X4 and antiserum ATH anti-ATL) with specificity for class II products of MHC subregions RT1.B and RT1.D, respectively. Adoptive transfer studies revealed that antibody and cytotoxic effectors (W3/25+, OX8+) with specificity for class II "Ia" determinants, though potentially injurious, are not required for rejection of cardiac allografts transplanted across isolated RT1.B/D disparities (RP leads to WF) because transfer even of small numbers (0.5 X 10(6] of helper T cells (W3/25+, OX8-) previously shown to be responsible for adoptive transfer of delayed type hypersensitivity to alloantigen, effected rejection in the absence of detectable antibody or Tc. In the immune response to alloantigen both cytotoxic T cell generation and a humoral immune response develop in parallel with that other form of cellular immunity, akin to classic delayed or tuberculinlike hypersensitivity, itself potentially a potent effector mechanism in organ allograft rejection.

Animals↗
PubMed2004

Borderline changes in the Banff schema: rejection or no rejection?

The relationship between acute renal allograft rejection and histopathologic biopsy alterations recognized by the Banff Schema as "borderline changes" is not clear. Some evidence supports the contention that about one third of patients with borderline infiltrates and clinical evidence of graft dysfunction do indeed have acute rejection, which, if left untreated, progresses to a histologically more advanced stage of rejection. Several investigators recognize that not all patients with mild tubulitis respond clinically to antirejection therapy; a significant number of these biopsy specimens display additional histological alterations. The most common concurrent lesions are chronic allograft nephropathy, arteriolar lesions consistent with calcineurin inhibitor toxicity, acute tubular necrosis, and obstructive nephropathy. Management of patients with borderline changes must tightly correlate the pathologic features and the clinical information.

Diagnosis, Differential↗
PubMed1978

The cellular basis of allograft rejection in vivo. I. The cellular requirements for first-set rejection of heart grafts.

The nature of the cells required for first-set graft rejection in vivo was examined by using an adoptive transfer system to restore heart-graft rejection in irradiated rats. Highly purified inocula of peripheral T lymphocytes were shown to quantitatively account for the restorative ability of adoptively transferred cells. These T cells were shown to be long-lived small lymphocytes which are not recently derived from the thymus during adult life. They belong to the pool of T cells which constantly recirculate from blood to lymph as shown by their rapid appearance in the lymph of iradiated syngeneic rats after intravenous injection. Neither B lymphocytes nor antibodies in the circulation or in the graft itself are required for first-set graft rejection.

B-Lymphocytes↗
PubMed1987

Rejection of bone marrow allografts by mice with severe combined immune deficiency (SCID). Evidence that natural killer cells can mediate the specificity of marrow graft rejection.

C.B-17 scid (H-2d) mice are homozygous for the gene that causes severe combined immune deficiency (SCID). These mice have no T or B cell function, yet display normal natural killer (NK) activity. Irradiated SCID mice were challenged with marrow grafts to determine if antibodies are necessary for marrow allograft rejection. SCID mice rejected H-2/Hh-1 allogeneic marrow grafts. Moreover, this rejection capability could be adoptively transferred using SCID marrow as a source of NK progenitors infused into irradiated B6 (H-2b) hosts. We conclude that NK cells can mediate marrow allograft reactivity in the absence of immunoglobulin. It follows that NK cells probably have specific receptors for Hh antigens.

Animals↗