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PubMed2002

Modeling chronic lung allograft rejection in miniature swine.

BACKGROUND: The success of lung transplantation has been limited by the perplexing problem of chronic rejection. The development of a large-animal model for the systematic study of the mechanisms underlying chronic lung rejection has been problematic. We have developed a new preclinical model of chronic lung rejection using MHC-inbred miniature swine. METHODS: Using standard operative techniques, four orthotopic left lung allografts were performed using MHC-matched, minor-antigen-mismatched donors. Recipient animals received a 12-day course of postoperative cyclosporine. Grafts were followed with open biopsies and high-resolution computed tomography. Cellular immune responses were monitored by mixed lymphocyte reaction, cytometric analysis of graft-infiltrating lymphocytes, and skin grafting. RESULTS: All grafts survived > or = 5 months and developed manifestations of chronic rejection, including obliterative bronchiolitis, interstitial fibrosis, and occlusive vasculopathy. A mononuclear infiltrate was also present in all grafts by the fourth posttransplant month. High-resolution computed tomography demonstrated several cardinal radiographic findings known to correlate with chronic rejection. Cytometric analysis of graft-infiltrating lymphocytes showed a predominance of CD8+ cells. The development of alloreactivity in the host was confirmed by mixed lymphocyte reaction and skin grafting. CONCLUSIONS: We report a reproducible, whole-lung, large-animal model of chronic lung rejection. In this immunogenetically defined construct, we have observed a full spectrum of histopathologic lesions that reproduce with fidelity those lesions observed in human lung transplant recipients suffering from chronic rejection. We anticipate that this preclinical model will facilitate further study of the pathogenesis and therapy of chronic lung rejection.

Animals↗
PubMed2002

Vascularized thymic lobe transplantation in miniature swine: I. Vascularized thymic lobe allografts support thymopoiesis.

BACKGROUND: Vascularized thymokidney transplants have previously been shown to induce tolerance across major histocompatibility complex barriers. The ability to perform vascularized thymic lobe transplantation could permit such tolerance to be induced with any cotransplanted solid organ or tissue. For this reason, we have developed a technique for vascularized thymic lobe transplantation in miniature swine. METHODS: Thymic vessels (n=2) were anastomosed to the carotid artery and the external jugular vein of naïve minor-mismatched recipients treated with a 12-day course of cyclosporine A (10 mg/kg/day). Graft survival and thymopoiesis were assessed by histology, immunohistochemistry, and fluorescence-activated cell sorting. Allele-specific antibodies 74-12-4 and pig allelic antigen (PAA) were used to distinguish donor and recipient cells. RESULTS: Allografts showed intact cortical and medullary structure posttransplantation, without evidence of rejection or ischemia. Recipient thymocytes repopulated the donor cortical thymus by POD30 and increased in the cortex and medulla by POD60. CONCLUSIONS: Our study demonstrates the technical feasibility of vascularized thymic lobe transplantation and the support of thymopoiesis by such transplants in a large animal model. This technique may offer a novel strategy to induce transplant tolerance across allogeneic and xenogeneic barriers, and to support long-term thymopoiesis in immunodeficient hosts.

Animals↗
PubMed1997

Central role of vascular smooth muscle hyperreactivity in coronary hyperconstriction after balloon injury in miniature pigs.

BACKGROUND: Coronary constrictive responses to autacoids become augmented 1 week after balloon injury in our swine model. The present study aimed to elucidate the mechanisms of this effect. METHODS: In 12 hypercholesterolaemic miniature pigs, the coronary constrictive response to serotonin was examined angiographically 1 week after injury. After the angiographic study, organ chamber experiments using excised coronary artery were performed to clarify whether functional changes in endothelial cells or in vascular smooth muscle cells contributed to the hyperconstriction. RESULTS: The coronary constrictive response to serotonin in vivo was significantly greater at the previously injured site than at the non-injured site. The degree of the hyperconstriction at the previously injured site exceeded that predicted from a geometric theory. Histological examination demonstrated that the previously injured site was almost covered with regenerated endothelial cells. In vitro studies demonstrated that serotonin caused significantly greater contraction in coronary artery strips, whether with or without endothelium, from the previously injured site than in those from the non-injured site. Endothelium-dependent relaxation in response to serotonin was comparable at the injured and non-injured sites. CONCLUSIONS: These results suggest that the coronary hyperconstriction response to serotonin 1 week after injury results primarily from hyperreactivity of vascular smooth muscle. Whereas any contribution of endothelial dysfunction or the geometric effect may be minimal.

Animals↗
PubMed2002

Mechanisms of chronic renal allograft rejection. II. Progressive allograft glomerulopathy in miniature swine.

We have reported that in thymectomized miniature swine treated with a 12-day course of cyclosporin A that major histocompatibility complex class I-mismatched renal allografts either progress to chronic rejection (progression group; n = 4) or tolerance after acute rejection (recovery group; n = 4). Two types of glomerulopathies, termed acute and chronic allograft glomerulopathy, occur in allografts in this model. Morphological and immunohistochemical studies were performed on serial renal biopsies from both groups to examine the pathogenic mechanisms of acute and chronic allograft glomerulopathy. In acute rejection, acute allograft glomerulopathy developed in both groups by Day 18, with antibody deposition and T cell and macrophage infiltration. In situ DNA nick end-labeling (TUNEL)+ injured glomerular endothelial cells appeared from the early phase, followed by destruction of the glomerular capillary network with segmental mesangiolysis. Thereafter, in the progression group, acute allograft glomerulopathy progressed to chronic allograft glomerulopathy during the development of chronic rejection. This process was associated with persistent T cell and macrophage infiltration, antibody deposition, and TUNEL+ glomerular endothelial injury in the glomeruli. Impaired capillary repair, mesangial cell proliferation, and activation were still noted at Day 100, together with accumulation of mesangial matrix and duplication of glomerular basement membrane. In contrast, in the recovery group, acute allograft glomerulopathy recovered by Day 100, associated with the resolution of cellular infiltration and reduction of antibody deposition. We conclude that the acute and persistent cell- and antibody-mediated rejection against glomerular endothelial cells is the key pathogenic determinant of acute allograft glomerulopathy and progression toward chronic allograft glomerulopathy. Impaired capillary repair and phenotypic change of endothelial and mesangial cells also contribute to the development of chronic allograft glomerulopathy. With the development of tolerance, substantial recovery of acute allograft glomerulopathy can occur after the resolution of glomerular inflammation.

Acute Disease↗
PubMed2003

Histocompatible miniature swine: an inbred large-animal model.

Three herds of miniature swine, each homozygous for a different set of alleles at the major histocompatibility complex (MHC), and five intra-MHC recombinant strains, have been reported by the authors' laboratory. One herd (SLAdd) was selected for further inbreeding to achieve a histocompatible line. It has undergone seven additional generations of sequential brother-sister or father-daughter matings (termed G7). To determine the level of histocompatibility of these animals, the authors performed skin and heart transplantation without immunosuppression. In contrast to MHC-matched, minor antigen-mismatched animals that rejected skin in 11 days (median survival time [MST], n=6) and hearts in 35 days (MST, n=4), G7 animals accepted skin for greater than 340 days (>340, >448, and >677 days) and hearts for greater than 265 days (>265 and >269 days). Nevertheless, rejection of second grafts could be induced by sensitization, indicating that weak minor antigens remain, requiring further inbreeding to achieve full histocompatibility. We conclude that G7 animals are sufficiently inbred to accept first set skin and heart grafts indefinitely.

Animals↗
PubMed2003

Spleen transplantation in miniature swine: surgical technique and results in major histocompatibility complex-matched donor and recipient pairs.

BACKGROUND: Spleen transplantation (Tx) between some strains of rodents can lead to donor-specific tolerance either spontaneously or after a short course of immunosuppression. This study developed a surgical technique for spleen Tx in miniature swine to investigate its immunologic impact in a large animal model. METHODS: The preferred surgical technique of spleen Tx (n=8) involved excision of the donor spleen with its vascular pedicle to the aorta and portal vein. Carrel patches of donor aorta and portal vein were anastomosed to the abdominal aorta and inferior vena cava, respectively, of the (splenectomized) recipient. The results in four major histocompatibility complex-matched pairs that were mismatched for the porcine allelic antigen are reported. Two recipients were untreated, one received a 12-day course of cyclosporine A (CsA) alone, and one received thymic irradiation (700 cGy) and CsA. Hematopoietic cell chimerism was followed by fluorescence-activated cell sorter, and graft survival was assessed by histology. RESULTS: Spleen Tx was technically successful. In two untreated pigs, chimerism was detected in the blood (maximum 5% for 17 and 25 days) and lymph nodes (maximum 6% for 28 and 56 days), but both grafts showed histologic rejection by day 28. In two treated pigs, chimerism was present in the blood for 47 and 57 days, and rejection was prevented, with follow-up for 57 and 217 days, respectively. CONCLUSION: Spleen Tx in major histocompatibility complex-matched pairs treated with CsA+/-thymic irradiation results in prolonged chimerism and is associated with the development of in vivo unresponsiveness to the transplanted spleen.

Animals↗
PubMed2003

Thymic transplantation in miniature swine: III. Induction of tolerance by transplantation of composite thymokidneys across fully major histocompatibility complex-mismatched barriers.

BACKGROUND: This study determines whether composite thymokidney (TK) grafts, created by implantation of autologous thymic tissue beneath the donor's renal capsule before transplantation, could induce allogeneic transplantation tolerance across two-haplotype fully major histocompatibility complex (MHC)- mismatched barriers in juvenile MGH-miniature swine. METHODS: TK grafts were prepared by implanting autologous thymic tissue under the renal capsule of donor animals 2 to 3 months before transplantation. Four recipients were treated with a T-cell-depleting immunotoxin and received fully MHC-mismatched TK grafts plus a 12-day course of cyclosporine A (CsA). Control animals were treated with CsA alone or both CsA and immunotoxin, but with a normal kidney or a kidney implanted with autologous lymph node rather than thymus. Renal graft function was assessed by plasma creatinine levels and histologic analyses. Immunologic status was monitored by cell-mediated lympholysis assays. RESULTS: All four recipients of fully MHC-mismatched TK transplants treated with immunotoxin and a 12-day course of CsA accepted their composite renal allografts long-term. All control recipients receiving a TK and CsA alone, a normal kidney or a composite kidney containing lymph node tissue acutely rejected their grafts. CONCLUSIONS: To our knowledge, this is the first demonstration that functional vascularized thymic grafts can induce transplantation tolerance across fully MHC-mismatched barriers in a large animal model.

Animals↗
PubMed2004

Posttransplant lymphoproliferative disease after allogeneic transplantation of the spleen in miniature swine.

Spleen transplantation (SpTx) was performed in miniature swine across full major histocompatibility complex barriers to study the tolerogenic effect of the spleen. This study describes the development of posttransplant lymphoproliferative disease (PTLD) after allogeneic SpTx. Recipient pigs underwent whole body irradiation (100 cGy), thymic irradiation (700 cGy), and native splenectomy (day 0), and received a 45-day course of intravenous cyclosporine (trough level 400-800 ng/ml). After SpTx, two of seven pigs developed PTLD (1 donor-type, 1 host-type). These two pigs had greater T cell depletion and higher trough levels of cyclosporine. Early changes that occurred prior to the development of clinical features of PTLD were increased porcine lymphotropic herpesvirus-1 viral loads in blood and tissues, and increased numbers of leukocytes, B cells, and total serum IgM. PTLD can occur after allogeneic SpTx in swine. This model may be useful in studies of the pathogenesis of PTLD.

Animals↗
PubMed2004

alpha1,3-Galactosyltransferase gene-knockout miniature swine produce natural cytotoxic anti-Gal antibodies.

BACKGROUND: The expression of galactose alpha 1,3 galactose (Gal) in pigs has proved a barrier to xenotransplantation. Miniature swine lacking Gal (Gal pigs) have been produced by nuclear transfer/embryo transfer. METHODS: The tissues of five Gal pigs of SLA dd haplotype (SLA) were tested for the presence of Gal epitopes by staining with the Griffonia simplicifolia IB4 lectin. Their sera were tested by flow cytometry for binding of IgM and IgG to peripheral blood mononuclear cells (PBMC) from wild-type (Gal) SLA-matched pigs; serum cytotoxicity was also assessed. The cellular responses of PBMC from Gal swine toward Gal SLA-matched PBMC were tested by mixed leukocyte reaction and cell-mediated lympholysis assays. RESULTS: None of the tissues tested showed Gal expression. Sera from all five Gal pigs manifested IgM binding to Gal pig PBMC, and sera from three showed IgG binding. In all five cases, cytotoxicity to Gal cells could be demonstrated, which was lost after treatment of the sera with dithiothreitol, indicating IgM antibody-mediated cytotoxicity. PBMC from Gal swine had no proliferative or cytolytic T-cell response toward Gal SLA-matched PBMC. CONCLUSIONS: Gal pigs do not express Gal epitopes and develop anti-Gal antibodies that are cytotoxic to Gal pig cells. The absence of an in vitro cellular immune response between Gal and Gal pigs is related to their identical SLA haplotype and indicates the absence of immunogenicity of Gal in T-cell responses. The model of Gal organ transplantation into a Gal SLA-matched recipient would be a valuable large animal model in the study of accommodation or B-cell tolerance.

Animals↗
PubMed2005

Role of the thymus and kidney graft in the maintenance of tolerance to heart grafts in miniature swine.

BACKGROUND: The authors have examined the mechanism whereby co-transplantation of a kidney and heart from the same donor induces and maintains tolerance to both organs in miniature swine. METHODS: Transplants were performed across a major histocompatibility complex class I mismatch, and recipients received cyclosporine for 12 days. Group 1 animals received heart transplants alone (n=5), and all other groups received both heart and kidney allografts. Group 2 animals received no further intervention (n=2). Group 3 animals underwent transplant nephrectomy 8 days after heart and kidney co-transplantation (n=2). Group 4 animals underwent transplant nephrectomy 100 days after co-transplantation (n=2). Skin grafts were placed on group 4 animals, on one group 3 animal, and on two animals from group 2. Group 5 animals underwent thymectomy 100 days after co-transplantation (n=4). RESULTS: Group 1 animals developed cardiac allograft vasculopathy (CAV) and rejection. Group 2 animals never developed CAV and demonstrated in vitro donor-specific unresponsiveness. Group 3 animals suffered CAV and rejection. Group 4 animals developed CAV without concomitant donor-specific cell-mediated lympholysis reactivity, interstitial rejection, or cessation of graft function. Skin grafts on group 3 and group 4 animals led to fulminant rejection of heart and skin grafts, in contrast to grafts on group 2 animals that had no in vivo effect. Group 5 animals developed CAV but no significant increase in interstitial infiltrates. CONCLUSIONS: Both the kidney and thymus were necessary for maintenance of tolerance to heart allografts.

Animals↗
PubMed2005

Combination treatment with donor-specific transfusions and cyclosporine a induces long-term survival of cardiac allografts in miniature Swine.

BACKGROUND: To evaluate whether pretransplant donor-specific transfusions (DST) can induce tolerance to cardiac allografts in large animals, heterotopic cardiac transplants were performed across a class I MHC barrier in inbred miniature swine. METHODS: Experimental animals received two DSTs, each containing 1.4x10 viable peripheral blood mononuclear cells, 14 and 7 days prior to transplantation together with a 12-day course of cyclosporine (CyA) (13 mg/kg IV) starting on postoperative day (POD) 0. RESULTS: Untreated (n=2) and DST-only (n=2) treated control animals rejected between POD 6 and 8. Animals treated with CyA alone (n=3) exhibited graft survival to 53, 52 and 59 days. In contrast, the combination of DST and CyA (n=3) led to stable graft function for >200 days. Long-term survivors maintained peripheral CML response against donor antigen. Following DSTs, the donor-specific proliferative response of CD8+ recipient T cells was significantly increased (P=0.011), and a significant number of CD8+ T cells underwent apoptosis (10.1% on POD 0; 5.2% on POD -14; P=0.04). None of the DST-treated animals developed donor-specific antibodies. CONCLUSIONS: These results are the first to demonstrate the ability of DST to induce operational tolerance to cardiac allografts in large animals, and they suggest that peripheral mechanisms of tolerance mediate this effect.

Acute Disease↗
PubMed2006

Role of the thymus in transplantation tolerance in miniature swine: V. Deficiency of the graft-to-thymus pathway of tolerance induction in recipients of cardiac transplants.

BACKGROUND: We have previously shown that both thymic immigrants (graft to thymus pathway) and thymic emigrants (thymus to graft pathway) are involved in tolerance to renal allografts in miniature swine treated with a short course of calcineurin inhibitors. This study investigates the role of these pathways in cardiac transplant survival in recipients treated with a short course of tacrolimus. METHODS: Eleven animals received two-haplotype fully MHC-mismatched cardiac grafts with a 12-day course of tacrolimus. Recipients were thymectomized on day -21 (n=5) or day 0 (n=3), or were left euthymic (n=3). Two of the day -21 thymectomized animals received a day 0 host-MHC matched thymocyte infusion. RESULTS: Euthymic recipients of cardiac grafts treated with an immunosuppressive regimen identical to that previously shown to induce tolerance in euthymic recipients of renal allografts all rejected their grafts. Although no animal became tolerant, animals that were euthymic or thymectomized on day 0, as well as recipients of day 0 host-type thymocyte infusions following thymectomy on day -21, developed donor-specific hyporesponsiveness and maintained their cardiac grafts for markedly prolonged periods. In contrast, all animals thymectomized on day -21 that did not receive thymocyte infusions developed strong antidonor CTL responses and rejected their grafts by day 35. CONCLUSIONS: The graft-to-thymus pathway that plays an important role in tolerance induction to renal allografts appears to be relatively deficient in recipients of cardiac grafts. Strategies to increase donor antigen migration to the host thymus might therefore assist in tolerance induction to cardiac allografts.

Animals↗
PubMed2006

Long-term acceptance of fully allogeneic cardiac grafts by cotransplantation of vascularized thymus in miniature swine.

BACKGROUND: We have previously reported the ability of both thymokidney and vascularized thymic lobe (VTL) allografts to induce transplantation tolerance to renal allografts across a full major histocompatibility complex (MHC) mismatch in thymectomized miniature swine. However, whether vascularized thymus is capable of inducing tolerance to less tolerogeneic organs when it is transplanted simultaneously is not yet known. The present study investigates cardiac allograft survival and the mechanism of long-term acceptance in recipient swine following cotransplantation of VTL and cardiac grafts from fully MHC-mismatched donors. METHODS: Animals received a heart graft, a heart graft and a VTL, or a heart graft and a donor thymocyte infusion. Immunosuppressive regimens consisted of 12 or 28 days of tacrolimus. RESULTS: All animals that received a VTL maintained their grafts significantly longer than their counterparts that received only a heart graft, and those receiving 28 days of tacrolimus maintained their heart grafts long-term. Recipients of a donor thymocyte infusion demonstrated slightly prolonged cardiac graft survival but all rejected their grafts, highlighting the importance of thymic stroma. Cytotoxic T-lymphocyte responses against third-party antigens by cells from tolerant animals showed restriction by both self and donor MHC, whereas responses of controls were restricted to self MHC only. The presence of donor dendritic cells in the VTL grafts and results of co-culture assays suggest that both central and regulatory mechanisms were involved in achieving long-term acceptance. CONCLUSION: This is the first demonstration of the long-term acceptance of fully MHC-mismatched cardiac allografts in large animals.

Animals↗
PubMed2007

Gene expression of porcine lymphotrophic herpesvirus-1 in miniature Swine with posttransplant lymphoproliferative disorder.

Porcine lymphotropic herpesvirus-1 (PLHV-1) is a gamma-herpesvirus related to Epstein-Barr virus (EBV) and associated with development of posttransplant lymphoproliferative disorder (PTLD) following allogeneic stem cell or spleen transplantation in miniature swine. Oligonucleotide microarrays were designed based on known open reading frames (ORFs) of PLHV-1. Expression was compared by cohybridization of cDNA from lymph nodes of PLHV-1+ swine after allogeneic spleen transplantation between either: 1) PTLD-affected and PTLD-unaffected swine; or 2) PTLD-affected swine vs. samples from the same animal prior to diagnosis. In PTLD-affected animals, consistent upregulation (nine ORFs) and downregulation (four ORFs) of PLHV-1 mRNA was observed in comparison to those without PTLD. No differences in gene expression were discovered at the time of clinical PTLD diagnosis compared to six to nine days prior to diagnosis in the same animals. This model provides insights into the pathogenesis of PTLD and, by extension, potential diagnostic and therapeutic tools for human EBV-associated PTLD.

Animals↗
PubMed2002

Fiber-optic confocal reflectance microscope with miniature objective for in vivo imaging of human tissues.

We have built a fiber-optic confocal reflectance microscope capable of imaging human tissues in near real time. Miniaturization of the objective lens and the mechanical components for positioning and axially scanning the objective enables the device to be used in inner organs of the human body. The lateral resolution is 2 micrometers and axial resolution is 10 micrometers. Confocal images of fixed tissue biopsies and the human lip in vivo have been obtained at 15 frames/s without any fluorescent stains. Both cell morphology and tissue architecture can be appreciated from images obtained with this microscope.

Biopsy↗
PubMed2003

A miniaturized neuroprosthesis suitable for implantation into the brain.

This paper presents current research on a miniaturized neuroprosthesis suitable for implantation into the brain. The prosthesis is a heterogeneous integration of a 100-element microelectromechanical system (MEMS) electrode array, front-end complementary metal-oxide-semiconductor (CMOS) integrated circuit for neural signal preamplification, filtering, multiplexing and analog-to-digital conversion, and a second CMOS integrated circuit for wireless transmission of neural data and conditioning of wireless power. The prosthesis is intended for applications where neural signals are processed and decoded to permit the control of artificial or paralyzed limbs. This research, if successful, will allow implantation of the electronics into the brain, or subcutaneously on the skull, and eliminate all external signal and power wiring. The neuroprosthetic system design has strict size and power constraints with each of the front-end preamplifier channels fitting within the 400 x 400-microm pitch of the 100-element MEMS electrode array and power dissipation resulting in less than a 1 degree C temperature rise for the surrounding brain tissue. We describe the measured performance of initial micropower low-noise CMOS preamplifiers for the neuroprosthetic.

Action Potentials↗
PubMed2005

Histopathology of spleen allograft rejection in miniature swine.

Spleen transplantation (SpTx) has established donor-specific tolerance in rodents, but not in large animals or humans. We report the histopathology of rejection in an established model of SpTx in major histocompatibility complex (MHC)-defined miniature swine. Of the 17 SpTx, rejection was observed in two grafts transplanted into untreated, MHC-matched, minor antigen-disparate recipients (group 1, n=4), but not in the two that received a 12-day course of cyclosporin A (CyA). Rejection also occurred in five grafts transplanted into fully MHC-disparate recipients (group 2, n=12), one of which was untreated and four of which received some form of immunosuppressive therapy. One recipient of an MHC class-I-mismatched spleen treated with 12 days of CyA did not show rejection. Following biopsy and/or necropsy, fixed allograft tissue sections were treated with multiple stains, immunohistochemical markers and TUNEL assay. Common features of rejection occurred in grafts from both groups, but with varying time courses. Necrosis developed as early as day 8 in group 2 and day 27 in group 1, ranging from focal fibrinoid necrosis of arteriolar walls and sinusoids to diffuse liquefactive necrosis, usually associated with haemorrhage. Other features of rejection included white pulp expansion by atypical cells and decreased staining of basement membranes and reticular fibres. A doubling of the baseline TUNEL index preceded histologically identifiable rejection. This study establishes histologic guidelines for diagnosing and, perhaps, in future studies, predicting acute rejection of splenic allografts transplanted across known histocompatibility barriers in a large-animal model.

Animals↗
PubMed1989

Genetic and other effects on antibody and cell mediated immune response in swine leucocyte antigen (SLA)-defined miniature pigs.

Miniature pigs of eight swine leucocyte antigens (SLA) haplotypes were immunized with sheep erythrocytes (SRBC), hen egg white lysozyme (HEWL) and the synthetic peptide (T, G)-A--L to induce antibody. Bacillus Calmette Geurin (BCG) and dinitrochlorobenzene (DNCB) were used to induce cell mediated immune response (CMI). Analysis of variance by least squares was used to assess the effects of SLA haplotype, sire, dam, litter and sex of pig on the magnitude of the primary and secondary antibody response and on dermal delayed type hypersensitivity induced by purified protein derivative of tuberculin (PPD) and DNCB-induced contact hypersensitivity. The statistical model accounted for 43.50-77.30% of the observed variability in antibody and CMI at various times after immunization or challenge. While SLA had a significant effect on both antibody and CMI to some antigens at some, but not all times, sire, dam and litter were more frequently significant and to a greater degree. Haplotypes dd, dg and gg produced more antibody to SRBC and (T, G)-A--L while dg and gg had higher primary, but not secondary antibody response to HEWL. Delayed hypersensitivity to PPD was most marked in pigs of dd, dg and gg haplotypes while contact hypersensitivity to DNCB was expressed least in the dg and gg haplotype pigs. Heritability estimates were high for response to (T, G)-A--L and HEWL indicating feasibility of selective breeding for these traits.

Analysis of Variance↗