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At least 19 recordsLinked to original sources

The course of pancreas allografts in rats conditioned by spleen allografts.

A new technique for transplanting duct-ligated rat pancreas grafts, rather similar to the technique for spleen grafting in rats, is presented. Inbred AGUS and WAG rats with a strong Ag-B incompatibility were used. Duct-ligated pancreas AGUS to AGUS isografts survived indefinitely in streptozotocin-induced diabetic hosts while WAG to AGUS allografts were quickly rejected. However, when WAG spleen and pancreas were transplanted en bloc to AGUS rats, endocrine pancreas graft function persisted for up to 6 weeks. This finding of a transient protection of pancreas allografts by donor-strain spleen allografts led to further experiments. AGUS recipients first received WAG spleen allografts which then were removed after 3 to 5 months, at which time WAG pancreas allografts were inserted. Sixty-eight per cent of these grafts survived and cured their hosts of streptozotocin-induced diabetes.

Animals

Graft-versus-host reactivity and renal allograft survival in rats given allogeneic spleen cells or spleen allografts.

Selective recruitment of antigen-sensitive cells (ASC) into the spleen as a method of inducing specific suppression was attempted by intravenous injection of either DA or Lewis spleen cells 24 hr before a (DA X Lewis)F1 renal allograft into a Lewis or DA recipient, either with or without a splenectomy. This led to suppression of rejection in the DA recipient and delayed rejection in the Lewis recipient. Splenectomy produced a minimal augmentation effect. Assay of graft-versus-host (GVH) reactions in (DA X Lewis)F1 rats by a popliteal node assay showed that injection of allogeneic DA or Lewis spleen cells 48 hr before the assay significantly reduced the reaction produced by node lymphocytes but not spleen lymphocytes, suggesting a loss of ASC from the lymph nodes. Lewis spleen allografts did not produce such a significant reduction in the GVH reactivity of DA node lymphocytes as intravenous Lewis cells, whereas DA spleen allografts led to an increased GVH reactivity of Lewis node lymphocytes. From these studies, it is not possible to attribute the suppression produced by the intravenous injection of allogeneic cells to selective recruitment of antigen-sensitive cells to the spleen.

Animals

Percutaneous needle biopsies of renal allografts: the relationship between morphological changes present in biopsies and subsequent allograft function.

In the Cambridge renal transplant unit percutaneous needle biopsies of renal transplants have been extensively used to help identify the cause of impaired allograft function. During the period 1966--1973, 154 of the 269 renal allografts transplanted were biopsied at least once during the first 90 days after transplantation. In this survey the relationship between morphological changes in these biopsy specimens and allograft function 1, 3 and 5 years after transplantation is assessed. A highly significant direct relationship exists between early graft failure and the presence of medial necrosis of arteries, acute glomerular lesions and interstitial haemorrhage. Less than 10% of grafts with one or more of these changes and none in which all three types of lesion were present were capable of supporting life at 1 year. There is a significant association between poor subsequent graft function and mononuclear cell infiltration of the intima of arteries. No clear relationship exists, however, between the function of grafts at 1 and 3 years and the degree of mononuclear cell infiltration of the interstitial tissue. Tubular necrosis was frequently observed and future graft performance is related to the extent and cause of the tubular damage.

Adolescent

Mixed leucocyte culture blocking factor activity in allograft recipients and its role in the clinical outcome of human cadaveric renal allografts.

Seventeen renal allograft recipients were followed serially both pre- and post-transplantation for the presence of mixed leucocyte culture blocking factor activity (MLC-BFA) in their plasma. Patients could be divided into three distinct groups on the basis of MLC-BFA and lymphocytotoxin (LT) determinations. Fifteen out of seventeen patients possessed MLC-BFA at one time or another while four out of seventeen were positive for LT. Four patients of group 1 with pre-transplant LT and MLC-BFA rejected their grafts within 1 year. Two LT negative patients of group 2 developed no detectable MLC-BFA during a follow-up period of over 1 year. One other patient developed MLC-BFA 8 months following transplantation. All three patients had an excellent clinical course. Ten patients belonging to group 3 possessed no LT or MLC-BFA prior to transplantation but developed MLC-BFA alone after receiving an allograft. Only one patient rejected his allograft within 2 months. The remaining nine patients experienced mild rejection crises during the first 3 months after transplantation but had excellent renal function at 1 year or beyond that time. Our results indicate that MLC-BFA in the presence of LT may not prevent rejection. MLC-BFA is associated with a good clinical course in LT negative patients. However, certain patients who fail to develop LT or MLC-BFA in spite of repeated blood transfusions prior to transplantation may also do extremely well in the absence of detectible MLC-BFA.

Adolescent

Cellular components of allograft rejection: identity, specificity, and cytotoxic function of cells infiltrating acutely rejecting allografts.

Functioning mononuclear cells have been harvested from heterotopic rat cardiac allografts during maximal transplant cellular infiltration. T cells, identified by a T cell-specific absorbed rabbit anti-rat brain serum, constituted two-thirds of the total cells recovered. Approximately 20% of the infiltrating cells bear and synthesize surface immunoglobulin. Macrophages, identified by latex ingestion and morphologic and cytochemical techniques, comprise 9% of the graft infiltrate. Donor-specific cytotoxic T lymphocytes are concentrated within the graft. A separate population of Fc receptor-positive recovered cells mediate antibody-dependent LMC (Ab-LMC). Neither effector cell was adherent or phagocytic. These studies have conclusively established that cytotoxic T lymphocytes accumulate within rejecting allografts; however, the enriched presence of cytotoxic T cells within the grafts is not fully dependent upon antigen recognition per se, since Lew animals grafted with both BN and BUF hearts have Lew anti-BN and Lew anti-BUF killer cells in each graft.

Animals

Immune responses to organ allografts. II. Decreased B cell responses to cardiac allografts in rats pretreated with enhancing, suppressor cell, or T lymphocyte depletion protocols.

Primarily vascularized LBN cardiac allografts transplanted to LEW rats are rejected 6 to 8 days after transplantation. Immunoperoxidase stains for cells producing immunoglobulin (Ig) demonstrate a proliferation of Ig-containing immunoblasts in the splenic red pulp (RP) and peripheral periarterial sheath (PAS) within 2 days after transplantation. These immunoblasts differentiate into plasma cells that triple the RP volume by the time of rejection. By 14 days, the plasma cells are replaced by mitotically active large and small lymphocytes with no demonstrable cytoplasmic Ig. Splenic Ig production is followed by a venous vasculitis in the graft and by the appearance of circulating cytotoxic antibodies 5 days after grafting. Three biological methods of prolonging cardiac graft survival were found to derange this sequence of immunological reactions at different stages. Enhancement by antigen and antibody pretreatment of the recipient elicited a premature production of Ig that subsided and was not reinitiated by cardiac transplantation. Transfer of suppression with thymocytes from enhanced cardiac recipients temporarily inhibited differentiation of splenic B cells into immunoblasts and plasma cells. T cell depletion by thymectomy, irradiation, and bone marrow reconstitution also decreased the plasma cell response, possibly by removing helper cells required to switch IgM production to IgG. These studies reemphasize the importance of Ig production in the complex interaction of immune reactions leading to acute rejection of organ transplants.

Animals

Sponge matrix allografts. A model for analysis of killer cells infiltrating mouse allografts.

A method for isolation of allograft-infiltrating cells in a functionally viable state is described in this article. The method is based on the use of a spongious tissue into which cells of strain A (e.g., fibroblasts or tumor cells) are grown. The resulting graft is then transplanted to a strain B animal, and the infiltrating cells are released from it by gentle compression. The graft-infiltrating cells are completely recovered, and they may be processed for further experimentation and analysis by employing exclusively physical methods of cell preparation. As an example of future applications, some preliminary results on density- and charge fractionation of the graft-infiltrating cells are also reported.

Animals

[Study of macrophages infiltrating rat cardiac allografts. II.--Cytoenzymatic analysis of cells infiltrating the grafts and of peritoneal macrophages in isograft and allograft recipients (author's transl)].

Cytoenzymatic analysis of cells infiltrating heart transplants in the rat confirms the high participation of monocytes and macrophages. However, when comparing iso and allografts, only slight differences are observed in the lysosomal enzyme specific colorations, whereas a striking difference in these colorations is found between heart infiltrates and peritoneal exsudates from these recipients. This could favour the hypothesis of a local macrophage activating process within the graft but seems more probably due to differences in cell maturation stages.

Acid Phosphatase

Fascicular nerve allograft evaluation. Part 2: comparison with whole-nerve allograft by light microscopy.

Orthotopic whole-nerve and fascicular nerve grafts were transplanted between inbred rats with known histocompatibility antigen structure. In general, the whole sciatic nerves demonstrated a graded rejection response dependent upon the degree of tissue histocompatibility differences. The fascicular grafts, however, had evidence of greatly decreased rejection and no stigma of a graded response dependent on degree of variability of tissue typing. Limitations of the experiment are outlined, and the possible avenues of further research are briefly discussed.

Animals