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 55 records · Page 3Linked to original sources
PubMed2000

The relationship between acute rejection and chronic rejection is highly dependent on specific MHC matching: a multi-strain rat heterotopic heart transplant study.

BACKGROUND: The impact of acute rejection, immunosuppression, and infection, specifically cytomegalovirus infection, on the development of chronic rejection in the cardiac allograft, has been the subject of a large number of investigations. One of the difficulties in finding associations has been the marked immunologic heterogeneity of the patient population coupled with the lack of the ability to HLA match. Furthermore, the ideal animal model, which duplicates as well as controls for this immunologic heterogeneity, is lacking. METHODS: To try to simulate differences in HLA matching, immunosuppression regiments and cytomegalovirus infection, heterotopic heart transplantation was performed in two separate, complete MHC mismatch, rat strain combinations (WF-LEW, BN-LEW) requiring chronic immunosuppression and employing four separate immunosuppression/infection protocols. Animals were followed for 6 months, killed, and rejection and vascular changes were scored blinded to the group. RESULTS: The mean vascular and acute rejection scores were not significantly different between treatment regiments for either specific strain combination. There was a trend for the subtherapeutic groups to have higher vascular scores. Overall, there were no significant differences in vascular scores between the WF-LEW and BN-LEW groups (1.25+/-0.18 vs. 1.13+/-0.20, P=NS). Similar numbers of WF-LEW and BN-LEW exhibited cellular infiltration and necrosis of the allograft, but the intensity of the response (rejection score) was more severe in the WF-LEW combination (4.54+/-0.22 vs. 3.92+/-0.21, P=0.052) when limiting the analysis to those with myocyte necrosis. There was no significant correlation between acute rejection and vascular lesion severity in the WF-LEW combination (r=0.22, P=NS) but a high correlation between these parameters in the BN-LEW combination (r=0.74, P<0.0001). CONCLUSIONS: These data suggest that, although acute rejection and chronic rejection are related, MHC matching may influence their interdependence. These data also may explain why the clinical association between acute and chronic rejection is difficult to demonstrate.

Acute Disease↗
PubMed2002

High transforming growth factor-beta and extracellular matrix mRNA response in renal allografts during early acute rejection is associated with absence of chronic rejection.

BACKGROUND: A case-control study was performed to investigate whether mRNA levels of transforming growth factor-beta (TGF-beta) and various extracellular matrix molecules in renal transplant biopsy specimens, taken during acute rejection episodes within 6 months of transplantation, discriminate between patients who show deterioration of graft function and develop chronic rejection (CR+ group), and those who do not develop chronic rejection (CR- group). METHODS: Patients in both the CR+ group (n=10) and the CR- group (n=18) had at least one biopsy-proven acute rejection episode within the first 6 months after transplantation. The two groups were similar with respect to donor-, recipient-, and transplantation-related clinical variables. Histologic changes (Banff classification) and the timing of the acute rejection episodes in the biopsies studied did not differ between groups. Renal cortical mRNA levels of TGF-beta1, collagen alpha1(IV), collagen alpha1(I), decorin, and the household gene glyceraldehyde-3-phosphate dehydrogenase in biopsy specimens taken during acute rejection episodes were quantified by real-time polymerase chain reaction. RESULTS: The mean TGF-beta mRNA level in the CR- group was 3.4 times higher than that in the CR+ group (P<0.04). The mean collagen IV, collagen I, and decorin mRNA levels in the CR- group were 4.2 times (P<0.05), 5.1 times (not significant), and 3.2 times (P<0.05) higher, respectively, than those in the CR+ group. The mean TGF-beta to decorin mRNA ratios between the two patient groups did not differ significantly. CONCLUSIONS: In summary, high mRNA levels for TGF-beta, collagen IV, and decorin, but not histopathologic changes, in biopsies taken during acute rejection episodes early after kidney transplantation are associated with absence of chronic rejection. We hypothesize that TGF-beta might have beneficial effects during acute rejection through its known antiinflammatory actions or as an inducer of tissue repair.

Acute Disease↗
PubMed2003

Synergistic effects of malononitrilamides (FK778, FK779) with tacrolimus (FK506) in prevention of acute heart and kidney allograft rejection and reversal of ongoing heart allograft rejection in the rat.

BACKGROUND: The effects of tacrolimus (FK506) and malononitrilamides (MNA) (FK778 and FK779) monotherapy and combination therapy were examined in prevention of acute heart and kidney allograft rejection and reversal of ongoing acute heart allograft rejection in the rat. METHODS: Brown Norway (RT1n)-to-Lewis (RT11) and ACI (RT1a)-to-Lewis (RT11) combinations were used, respectively, for heart and kidney transplantation models. Immunosuppressants were administered orally from day 1 to day 14 for preventing acute rejection and from day 4 to day 34 after transplantation for the reversal of ongoing acute rejection. RESULTS: In the prevention of acute heart rejection model, recipient rats treated with monotherapy of tacrolimus or MNA (FK778, FK779) showed a dose-related prolongation of mean survival time (MST) compared with naive control rats (P<0.01). The mean survival time in combination therapy of tacrolimus (FK506) and FK778 indicated that an additive to synergistic interaction was produced when compared with the respective monotherapies (combination index [CI]=0.631-1.022). These results were reproducible with tacrolimus and FK779 combination therapy (CI=0.572-0.846). Furthermore, similar results were also found in the prevention of acute kidney allograft rejection in the rat (CI=0.137-0.516). In the reversal of ongoing acute heart allograft rejection, combination therapy of tacrolimus and FK778 demonstrated a strong synergistic interaction (CI=0.166-0.970) compared with monotherapy of tacrolimus or FK778. CONCLUSIONS: Combination therapy of tacrolimus and MNA (FK778, FK779) produces synergistic effects in prevention of acute heart and kidney rejection and reversal of ongoing heart allograft rejection in the rat.

Acute Disease↗
PubMed1999

Clinical rejection is distinguished from subclinical rejection by increased infiltration by a population of activated macrophages.

It has been reported previously that one-third of protocol renal biopsies in asymptomatic, biochemically stable renal transplant recipients in the first 6 mo show unsuspected subclinical graft rejection (both infiltrate and tubulitis) and that subclinical rejection is a risk factor for chronic renal dysfunction. This study was performed to determine whether differences in phenotype or activation status of graft-infiltrating cells underlie these different manifestations of acute rejection. Biopsies with normal histology (n = 10), subclinical rejection (n = 13), and clinical rejection (n = 9) were studied using immunohistochemistry and computerized image analysis. Subclinical and clinical rejections had similar histologic Banff scores. Univariate analysis showed a trend for a higher infiltration with CD8+ (P = 0.053) and CD68+(P = 0.06) cells in clinical rejection. Of the activation markers studied (CD25, perforin, tumor necrosis factor-alpha), only allograft inflammatory factor-1+-activated macrophages were significantly (P = 0.014) increased in the infiltrate of clinical rejection biopsies. These data suggest that activated macrophages or their products are responsible for acute renal dysfunction associated with clinical rejection episodes.

Acute Disease↗
PubMed2002

[Effect of acute rejection episode on occurrence of chronic rejection after kidney transplantation].

Chronic rejection is the most prevalent cause of renal transplant failure in the late post-transplant period. The clinical significance of acute rejection episodes on occurrence of chronic rejection is controversial. We analyzed 503 cases of the first renal transplantation maintained by calcinurine inhibitor for the correlation of acute rejection and clinical chronic rejection. The later the first episode of acute rejection occurred, the shorter was the half-life of graft. The acute rejection occurring within 3 post-transplant months worsens long-term graft survival if the peak creatinine level exceeds 2 mg/dl. Multivariate analysis by the Cox proportional hazard model for factors affecting cadaver graft loss by chronic rejection, revealed that the risk factor of acute early rejection was lower than those of donor age and post-transplant hypertension.

Acute Disease↗
PubMedDate not supplied

Management of rejection in heart transplant recipients: does moderate rejection always require treatment?

Triple-drug immunosuppression with cyclosporine, azathioprine, and steroids was introduced at Papworth Hospital in 1986. The management of rejection episodes in the first 40 patients receiving this regimen was reviewed for a minimal follow-up period of 18 months. Routine endomyocardial biopsy specimens were taken and classified into nil, minimal, mild, moderate, and severe rejection categories. Management was dependent on the biopsy result, in addition to the clinical state of the patient. In the early postoperative period (day 0 to 30) 2% of biopsy results showed severe rejection and 27% showed moderate rejection; all but one of the latter patients received augmentation of immunosuppression. In the intermediate period (days 31 to 90) severe rejection was present in 1% and moderate rejection in 36 (31%) of biopsies. Immunosuppression was augmented in 13 symptomatic patients, but in 23 asymptomatic patients additional therapy was withheld and the biopsy was repeated in 5 to 7 days. If moderate rejection was still present (11 cases), immunosuppression was augmented. Later (3 to 12 months) augmentation of immunosuppression was given on only four occasions. When the histologic criteria for diagnosis of moderate rejection are present during the early period after transplantation, we recommend augmented immunosuppression. In cases of later rejection we suggest that the decision be based on the biopsy result and the clinical condition of the patient; however, a prospective controlled trial will be required to confirm that this policy is correct.

Adolescent↗
PubMed1985

Experimental pancreas allograft rejection: correlation between histologic and functional rejection and the efficacy of antirejection therapy.

In this study the sequence of histologic changes in rejecting pancreatic allografts was correlated with the recurrence of hyperglycemia to evaluate the usefulness of serum glucose monitoring in pancreas transplantation. In addition, various immunosuppressive agents were evaluated for their efficacy in reversing rejection. Diabetic (streptozocin) Lewis rats were recipients of histoincompatible Lewis X Brown Norway F1 pancreatic grafts, which uniformly resulted in a fall in serum glucose levels from greater than 400 mg/dl to less than 150 mg/dl. Specimens were examined daily from the time of transplantation to determine the time of earliest histologic rejection. Functional rejection was defined as a rise in serum glucose levels to greater than 200 mg/dl and occurred at 8.5 +/- 0.8 days in the control group. Histologic evidence for rejection was present by day 3 as a perivascular lymphoid infiltrate while islets remained normal. Extensive cellular rejection of the exocrine tissue occurred by day 6 when most recipients were still normoglycemic. Complete pancreatic destruction was present by day 9. Antirejection therapy with methylprednisolone (MP), antithymocyte serum (ATS), or cyclosporine (CS) started at the time of recurrent hyperglycemia (days 8 or 9) and was uniformly unsuccessful in prolonging graft survival, with mean survival times of 8.3 +/- 0.8 (MP), 9.0 +/- 0.7 (ATS), and 9.3 +/- 0.4 (CS). In contrast, either ATS or CS but not MP begun on day 3, when histologic rejection was first observed, significantly prolonged graft survival to greater than 11 days in most recipients. We conclude that islet destruction is irreversible by the time that marked elevation in serum glucose levels occurs and therefore a more sensitive measure of pancreas rejection is needed. Furthermore, ATS and CS are more effective than are corticosteroids in reversing early rejection.

Animals↗
PubMed1994

Acute rejection of marrow grafts in mice. Dependence on and independence of functional TCR in the rejection process.

The question of how irradiated mice acutely reject marrow grafts has remained controversial, and evidence in support of T cell- and natural killer cell-mediated rejection mechanisms has been provided. Here we show in support of previous data that CB17 severe combined immunodeficiency mice acutely reject allogeneic marrow but the specificity of rejection cannot be mapped within the MHC. It is shown that a similar rejection specificity is also expressed in normal CB17 mice and that it is caused by CD3- or CD3+ effector cells that do not utilize TCR. In search of TCR-independent rejection mechanisms in other mouse strains, use is made of TCR transgenic mice expressing a defect in recognizing H-2Dd. It is shown that, although marrow graft rejection is impaired in these mice, pointing to participation of TCR in the rejection process, residual resistance does exist. This resistance maps to the MHC, cannot be shown to involve TCR, and appears to be expressed by NK1+ CD3+ cells. It is concluded that acute marrow graft rejection in normal mice can be mediated by both TCR-mediated and NK cell receptor-dependent effector mechanisms, depending on the particular mouse strains.

Acute Disease↗
PubMed1995

Rejection of mouse melanoma elicited by local secretion of interleukin-2: implicating macrophages without T cells or natural killer cells in tumor rejection.

Tumor cells transduced with cytokine genes provide a model to study host-effector mechanisms involved in tumor rejection. Local IL-2 production within a tumor site mimics a specific helper-T-cell response, bypassing an immunization phase. Growth of mouse B16F10 melanomas transduced with interleukin-2 (IL-2) in syngeneic hosts were significantly delayed. IL-2-producing B16F10 cells were super-transduced with interferon-gamma to up-regulate expression of major-histocompatibility-complex (MHC) antigens. Expression of class-I- or class-II-MHC molecules did not augment tumor rejection of IL-2-secreting tumor cells. Rejection of IL-2-transduced B16F10 cells in syngeneic mice was unaffected by depletion of CD8+ T-cell and NK1.1+ natural-killer (NK) cell populations. Tumor rejection occurred in SCID mice even after depletion of NK1.1+ cells, confirming that T cells and NK cells were not required for tumor rejection. Histologic examination of sites of tumor rejection showed inflammation, characterized by infiltrates of macrophages, occasional neutrophils, and areas of necrosis. When mice were treated systemically with macrophage-colony-stimulating factor to expand monocyte pools, tumor rejection was significantly augmented further. This study shows that in situ IL-2 production can result in tumor rejection mediated by inflammatory events, possibly involving macrophages, and mimicking a delayed-type hypersensitivity (DTH) response even in the absence of T cells and NK cells. Furthermore, tumor rejection can be enhanced by systemic administration of a cytokine to expand potential inflammatory cell populations.

Animals↗
PubMed1996

S RNase and Interspecific Pollen Rejection in the Genus Nicotiana: Multiple Pollen-Rejection Pathways Contribute to Unilateral Incompatibility between Self-Incompatible and Self-Compatible Species.

In self-incompatible (SI) plants, the S locus acts to prevent growth of self-pollen and thus promotes outcrossing within the species. Interspecific crosses between SI and self-compatible (SC) species often show unilateral incompatibility that follows the SI x SC rule: SI species reject pollen from SC species, but the reciprocal crosses are usually compatible. The general validity of the SI x SC rule suggests a link between SI and interspecific pollen rejection; however, this link has been questioned because of a number of exceptions to the rule. To clarify the role of the S locus in interspecific pollen rejection, we transformed several Nicotiana species and hybrids with genes encoding SA2 or SC10 RNase from SI N. alata. Compatibility phenotypes in the transgenic plants were tested using pollen from three SC species showing unilateral incompatibility with N. alata. S RNase was implicated in rejecting pollen from all three species. Rejection of N. plumbaginifolia pollen was similar to S allele-specific pollen rejection, showing a requirement for both S RNase and other genetic factors from N. alata. In contrast, S RNase-dependent rejection of N. glutinosa and N. tabacum pollen proceeded without these additional factors. N. alata also rejects pollen from the latter two species through an S RNase-independent mechanism. Our results implicate the S locus in all three systems, but it is clear that multiple mechanisms contribute to interspecific pollen rejection.

Journal Article↗
PubMed1984

Immune rejection mechanisms in murine leukemia. I. Timing of tumor cell rejection process relative to the development of humoral and cell-mediated cytotoxic immune responses.

Studies were undertaken to investigate the relationship between cell-mediated and humoral immune responses in the rejection of L1210/MTX-Rev (LR) leukemia cells in CD2F1 mice. The anti-LR antibody (humoral) response was defined by both its cytotoxic antibody titer and isotype composition, assessed by a complement-dependent cytotoxicity assay and radioimmune assay, respectively. The cytotoxic thymus (T)-derived lymphocyte response in the spleen was quantitated by 125I release by 125I-IUdR-labelled target cells. Analysis of the sera of tumor-bearing mice indicated that the LR leukemia cells elicited a wide spectrum of anti-tumor antibody isotypes. In mice that mounted a rejection response, the IgM anti-LR response was transient, while in those that did not, the IgM response persisted. Antibody titers for all isotypes remained low until the onset of LR rejection. At that time, high titers of IgG anti-LR antibodies, predominantly of the IgG2a subclass, were detected in sera of tumor-free mice. Thus, the LR rejection response coincided best with the appearance of high titers of IgG2a anti-LR antibodies. A single i.p. injection of viable LR cells elicited a potent cell-mediated immune response; neither the appearance nor the magnitude of the cell-mediated immune response as measured in the spleen correlated well with the onset or the strength of the LR rejection response in the peritoneal cavity. The LR peritoneal cell population grew unabated in the presence of an intense spleen cell-mediated immune response, and the rejection process began at a time when little cellular immunity could be detected. These results suggest that in the rejection response IgM antibodies contribute little, if any, to the process, and the role of cytotoxic T lymphocytes is questionable (uncertain). The rejection of LR cells appears to be primarily mediated by IgG2a antibodies.

Animals↗
PubMed1988

The use of OKT3 in cadaveric renal transplantation for rejection that is unresponsive to conventional anti-rejection therapy.

Thirty-one recipients of cadaver kidney transplants were given OKT3 monoclonal anti-T cell antibody for rejection treatment after conventional therapy had failed. Seventy-four percent of steroid or steroid and antithymocyte globulin (ATG) resistant rejections reversed with a standard course of OKT3. Rejections reversed in 85% of 26 patients treated within 90 days of transplantation. Late rejections treated more than 90 days after transplantation were poorly responsive to OKT3 and graft survival for this group of five patients was poor (20%). However, for those patients treated with OKT3 for early resistant rejection, actuarial 4-year graft survival was 66%. Actuarial 4-year patient survival was 97%, and the incidence of serious infection was low. Acute rejections in cadaver transplantation are common and a small percentage of rejections are resistant to steroids and ATG. OKT3 has proven to be useful for reversing these resistant rejections without causing significant morbidity from infection or death.

Adolescent↗
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↗
PubMed1983

The cellular basis of allograft rejection in vivo. III. Restoration of first-set rejection of heart grafts by T helper cells in irradiated rats.

An adoptive transfer model was used to examine the subpopulations of lymphocytes required to effect first-set rejection of directly vascularized heart allografts. PVG heart grafts are not rejected in irradiated DA hosts for at least 50 days. The adoptive transfer of 5 X 10(7) syngeneic lymph node cells (LNC) restores rejection to 14.4 +/- 2.4 days (mean +/- SD). Subpopulations of LNC, were separated by an indirect "panning" technique using the mouse antirat monoclonal antibodies W3/13, MRC OX8, or W3/25 to deplete the unwanted subsets of cells. Each subpopulation was tested, in a number equivalent to the number present in 5 X 10(7) normal LNC, for its ability to cause the rejection of heart grafts. Whole T cells (W3/13+) or helper/inducer T cells (W3/25+) restored graft rejection to 16.4 +/- 3.8 d and 16.0 +/- 2.4 days, respectively. Neither cytotoxic/suppressor T cells (MRC OX8+) nor B cells (Ig+) restored rejection. Indirect immunoperoxidase stains of the grafts showed that although W3/25+ cells predominated in the rejected tissue, MRC OX8+ cells were also present even in grafts from rats restored with inocula that contained less than 1% MRC OX8+ cells. Examination of lymphoid tissues suggested that the MRC OX8+ cells might be of host origin. By the time the grafts were rejected in irradiated hosts, significant thymic regeneration had occurred and there were large numbers of MRC OX8+ cells present in the thymus, as well as some in lymph nodes and spleen.

Animals↗
PubMed1985

Immune mechanisms in organ allograft rejection. VI. Delayed-type hypersensitivity and lymphotoxin in experimental renal allograft rejection.

The cellular requirements for renal allograft rejection have been reassessed in a rat adoptive transfer model, preceding studies having shown that transplanted kidneys may be rejected in the absence of cytotoxic T cells or specific antibody. Unilaterally nephrectomized, sublethally irradiated (780 rads) LEW recipients of renal allografts from irradiated WF donors, were selectively reconstituted with spleen cells from sensitized syngeneic donors and subjected to delayed nephrectomy of the residual native kidney 3 days posttransplantation. In some experiments the reconstituting inocula were depleted of SIg+ cells (anti-Ig column) or additionally depleted of cytotoxic T cells and their precursors reactive with monoclonal OX8 (rosette depletion). Depleting the reconstituting inocula of SIg+ cells as well as cells reactive with monoclonal OX8 failed (n = 4) to alter the tempo of rejection, as demonstrated by a mean serum creatinine +/- SD on day 8 of 5.4 +/- 3.8 vs. 6.4 +/- 4.2 in recipients (n = 8) reconstituted with unfractionated inocula. These data support a link between DTH and graft rejection, so additional studies were performed to characterize rat lymphotoxin (LT), one of the potential mediators of DTH-induced tissue injury, and to demonstrate the presence of LT in rejecting rat renal allografts. Rat LT, generated in vitro by stimulating spleen cells from specifically sensitized rats with keyhole limpet hemocyanin (100 micrograms m/ml), was shown on gel filtration to have an MW of approximately 50,000. In-vitro-generated rat LT was shown to be heat stable (70 degrees C for 15 min) and soluble in 40% (NH4)2SO4. Rat LT eluted as a single peak on DEAE anion exchange chromatography (0-0.15 M, NaCl osmotic gradient), supporting the existence of but a single molecular form. LT was isolated from rejecting renal allografts on day 6 after renal transplant but undetected (less than 1 unit) in residual native kidneys. This study, therefore, provides substantial support for a link between DTH and renal allograft rejection. Lymphotoxin, one of the potential mediators of tissue injury in this model system, has been partially characterized and demonstrated to be present in rejecting rat renal allografts.

Animals↗
PubMed1985

Graft rejection in a congenic panel of rats with defined immune response genes for MHC class I antigens. I. Rejection of and priming to the RT1Aa antigen.

Allograft rejection in the rat has been shown to be under stringent immune response (Ir) gene control using major histocompatibility complex recombinant animals as donors. Presentation of an isolated class I antigenic difference to high responder recipients results in rapid graft rejection, but low responders fail to reject. This striking qualitative difference is also seen in some liver grafting experiments in which the donor presents a full MHC haplotype and minor antigen mismatch to the responders. Grafts of other organs, however, do not discriminate qualitatively between high and low responders when a full haplotype mismatch exists. We have used the canonical high and low-responder animals, (PVG X PVG-RT1u)F1 and PVG to examine whether any qualitative difference in responsiveness can be detected against the a haplotype using a variety of organ grafts. We have confirmed a qualitative difference between high and low responders using PVG.R1 donors presenting an isolated class I (Aa) difference. Rapid rejection by high responders contrasted with complete failure to reject by the low responders. No difference in rejection tempo was found when a full a haplotype mismatch was introduced. This could have reflected vigorous responses to I and C region differences, because rapid rejection through these regions was demonstrated using the PVG.r1 (AaIcCc) and PVG.r8 (AaIuCu) recombinants. The feeble immunogenicity of the Aa antigen for PVG animals was revealed by priming and cross-priming experiments showing not only that r1 failed to prime for subsequent r1 graft rejection, but that the Aa antigen presented in concert with Ia and Ca also failed to prime. An unexpected result was that the Aa antigen of r1 actually suppressed responsiveness, especially when delivered by a heart graft. This suppression not only extended to subsequent r1 grafts (for example, skin rafts) but also to subsequent grafts of a tissue. The mechanism of this suppression remains unclear but preliminary experiments argue in favor of enhancement rather than active suppression.

Animals↗