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S J Prowse

Publications and source records attributed to S J Prowse.

At least 37 records · Page 2Linked to original sources
PubMed1986

Desferrioxamine treatment prevents chronic islet allograft damage.

BALB/cByJ islet allografts are acutely rejected when transplanted into allogeneic mice (CBA/J). Culture of the tissue for 7 days in 95% O2 before grafting is a suboptimal treatment for the reduction of immunogenicity in this strain combination. Approximately half the animals reject these transplants in a chronic fashion. Chronic islet rejection differs from acute rejection of uncultured allogeneic islets. During chronic rejection, beta cells within the transplanted tissue degranulate but remain intact when the animal returns to the diabetic condition. Acute islet rejection is characterized by the destruction of beta cells that remain heavily granulated as long as they remain intact. We examined the effect of the iron chelating agent, desferrioxamine, on chronic islet allograft damage. Desferrioxamine inhibited chronic islet allograft damage but did not influence the process of rejection of uncultured islet tissue. This effect of desferrioxamine could not be attributed to a direct immunosuppressive effect of this agent.

Animals↗
PubMed1985

Pancreatic islet allograft function in nonimmunosuppressed conscious mice.

CBA/H (H-2k) male mice were made diabetic by giving Streptozotocin 300 mg/kg intravenously. They were transplanted beneath the renal capsule with seven clusters of BALB/c (H-2d) adult islets, cultured for seven days in 95% O2 and 5% CO2. Basal blood glucose and weight gain returned to normal within 7 to 10 days. Blood glucose and serum insulin responses to intragastric glucose, intraperitoneal arginine and intraperitoneal theophylline were assessed after restoration of normoglycemia and compared with the responses in a control group of CBA mice. The animals were pretreated with intraperitoneal phentolamine and propranolol to reduce the stress of these procedures. Essentially normal carbohydrate tolerance was maintained in the transplanted animals but the insulin responses were markedly reduced, suggesting an increased sensitivity to insulin. The insulin content of the grafted tissue was also found to be considerably lower than that in the normal pancreas. This study demonstrates that in the mouse, adult pancreatic islet allografts can respond to stimuli that require functional adaptation by the islets. Further studies are required in larger animals before islet transplantation can be applied to the management of insulin dependent diabetic patients.

Animals↗
PubMed1985

T lymphocyte function in vivo. Ambivalence of the class I MHC antigen-reactive subset.

Lymphocytes that recognize class I alloantigens (class I T cells) are able to lyse appropriate target cells and release lymphokines in vitro. However the relative contribution of these activities to biological, in vivo functions of these cells is unclear. It is possible to discriminate between these activities using cyclosporine (CsA). CsA inhibits lymphokine release from class I T cells but has no effect on their cytotoxic activity. The in vivo function of class I T cells is analyzed using 2 models; the local GVHR induced by the transfer of sensitized T cells to the foot-pad and islet allograft rejection induced by the passive transfer of sensitized T cells. Both reactions may be mediated by class I T cells. CsA inhibits the in vivo functions of the class I T cells in both systems--hence, these functions appear to be lymphokine-dependent. This demonstrates the ambivalence of this T cell subset in relation to biological function; the cells express direct cytotoxic activity and producing lymphokines. The alloreactivity of the class I T cells is dependent upon the latter activity.

Animals↗
PubMed1983

Immunoglobulin-deficient rats fail to develop experimental allergic encephalomyelitis.

Lewis rats were treated from day of birth with a rabbit anti-rat IgM antiserum. As adults these animals were found to have no detectable serum IgM and greatly reduced levels of IgG. They failed to respond to the B-cell mitogen LPS, or to make antibodies to sheep red blood cells (SRBC) or myelin basic protein (BP). These B-lymphocyte and immunoglobulin-deficient rats failed to develop clinical or histological evidence of EAE when sensitized with either whole spinal cord or purified BP. That some T-cell functions of these suppressed animals were not altered was seen by their ability to respond normally to PHA and to reject tissue allografts. The results would suggest that B-cell function (immunoglobulin-antibody production) is essential for the induction of EAE.

Agammaglobulinemia↗
PubMed1983

Stabilization of islet allografts by treatment of recipients with ultraviolet irradiated donor spleen cells.

Culture of mouse pancreatic islets in an oxygen-rich atmosphere before transplantation facilitates long-term allograft survival without the use of immunosuppression. A comparison of the capacity of ultraviolet (UV) irradiated and live spleen cells of donor origin to induce allograft rejection showed that UV-irradiated spleen cells were not immunogenic; live spleen cells were immunogenic and their injection triggered allograft rejection. Following treatment with irradiated spleen cells from about day 30 post-transplantation, recipient animals were able to withstand subsequent challenges with 10(6) and 10(7) viable donor spleen cells. Untreated animals rejected their graft when challenged with 10(6) donor spleen cells. That is, treatment with UV-irradiated cells stabilized the islet allograft by inducing a state of tolerance. Subsequent transplantation of stabilized animals with uncultured thyroids of both donor origin and from a third party strain demonstrated that the tolerance was specific. In vitro test of immune reactivity showed this tolerance was not due to the deletion of antigen reactive cells.

Animals↗
PubMed1983

Cultured thyroid allografts induce a state of partial tolerance in adult recipient mice.

Thyroid allografts (BALB/c) prepared for transplantation by cyclophosphamide pretreatment of the donor, followed by organ culture of donor tissues for 3 weeks in a gas phase of 95% O2-5% CO2 function in normal CBA recipient mice for greater than or equal to 350 days. Up to 100 days post-transplantation, the tissue can be rejected by challenge of the recipient with 10(5) BALB/c peritoneal cells. After prolonged residence in the recipient (greater than 100, less than or equal to 350 days), only a proportion of allografts are rejected when the recipient is challenged with 10(5) followed by 10(6) peritoneal cells of donor origin. Recipients of long-term allografts are partially tolerant of BALB/c tissues. They are hyporesponsive to in vivo challenge with BALB/c spleen cells. However, lymph node cells from these animals respond essentially normally to stimulation with BALB/c spleen cells in vitro. Tolerant recipients will accept a second uncultured BALB/c allograft after a transitory rejection crisis. This crisis is not observed in the primary allograft.

Aging↗
PubMed1982

Resistance of established islet allografts to rejection by antibody and complement.

Using preliminary in vitro culture in an oxygen-rich atmosphere to facilitate survival of the graft, long term survival (greater than 100 days) of mouse pancreatic islet allografts was obtained subsequently in non-immunosuppressed diabetic animals. When anti-donor alloantiserum was transferred to these animals, the grafts were not rejected despite the fact that circulating cytotoxic antibody was demonstrated up to 7 days after injection of alloantiserum. Similarly, there was no graft rejection following the injection of anti-donor alloantiserum and complement. These results show that cultured islet allografts are not susceptible to antibody and complement.

Animals↗
PubMed1982

Islet allografting without immunosuppression: reversal of insulitis-associated diabetes and a case of spontaneous juvenile onset diabetes in mice.

The development of juvenile onset diabetes may involve an autoimmune response causing an insulitis and beta cell destruction. It has been suggested that replacement of the host's beta cells by transplantation may lead to the destruction of the new tissue by the same processes which caused the destruction of the original beta cells. This study does not support this proposal. It was possible to reverse insulitis-induced diabetes and spontaneous murine 'juvenile onset' diabetes by transplantation of cultured islet allografts. The grafts survived and maintained normoglycaemia for periods in excess of 100 days.

Animals↗
PubMed1982

Interleukin 2 secretion by sensitized cells from mice infected with Nematospiroides dubius: kinetics and specificity of the response.

The lymphokine Interleukin 2 (IL2) is secreted by T lymphocytes from mice infected by the murine parasitic nematode Nematospiroides dubius upon in vitro re-stimulation by specific parasite antigens. This study showed that the lymphocytes secreting IL2 were located in the lymphoid tissues draining the site of infection as well as in the spleen and peritoneal cavity of infected mice. There were marked fluctuations in the numbers of IL2 secreting cells in the posterior gastric lymph nodes and the peritoneal cavity at various times following single or multiple infections. However, there was no correlation between the appearance of IL2 secreting cells in infected mice and the development of resistance to re-infection by third stage larvae (L3). The specificity of the IL2 response for N. dubius antigens was demonstrated by the finding that antigen preparations from other helminths did not stimulate a response. It was also found that living but not killed N. dubius L3 could stimulate IL2 secretion, emphasizing the importance of living L3 in the induction of resistance to re-infection.

Animals↗
PubMed1982

The reversal of diabetes by pancreatic islet transplantation.

In this paper the theoretical basis of alloreactivity and its relevance to transplantation biology is discussed prior to a review of work showing that culture of adult mouse pancreatic islets for 7 days in 95% O2 and 5% CO2 facilitates successful grafting to nonimmunosuppressed allogeneic recipients. These allografts function by reversing both chemically induced and spontaneous diabetes. The fetal mouse pancreas is more immunogenic than adult islets, and even after a culture period of 10 days in 95% O2 and 5% CO2, BALB/c allografts are consistently rejected by nonimmunosuppressed recipient mice. The immunogenicity of fetal pancreas is thought to be due to the presence of contaminating lymphoreticular cells in the mesentery surrounding the fetal pancreas. Digestion of the fetal pancreas with collagenase allows the isolation of proislets that develop into functional islet tissue on transplantation. Fetal proislets are less immunogeneic than the whole fetal pancreas and may provide a source of tissue for clinical transplantation. Established islet allografts are relatively stable and are not rejected following nonspecific stimulation of the recipient's immune system or following passive transfer of either antibody or antibody and complement. After prolonged residence in the recipient a state of allograft tolerance develops and such grafts resist rejection by specific stimulation of the recipient. The administration of donor antigen in the form of uv-irradiated cells enforces this state of allograft tolerance.

Age Factors↗