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Biomedical subjects

K J Lafferty

Publications and source records attributed to K J Lafferty.

At least 109 records · Page 6Linked to original sources
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

The isolation and transplantation of foetal mouse proislets.

A method is described for the isolation of "proislets' from mouse foetal pancreas. Histologically, isolated proislets are composed of undifferentiated tissue which does not stain with aldehyde fuchsin. Following isotransplantation, proislets develop into well differentiated islets with beta cell granulation. In addition, isografts consisting of proislets harvested from 8 foetal mouse pancreases have the functional capacity to reverse Streptozotocin-induced diabetes. Proislets appear to represent foetal precursor islet tissue.

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

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↗
PubMed1982

Lethal effect of the intravenous injection of H-2 alloantigen activated T cells.

T cells of C57BL/6J (B6) mice activated in vitro against the K and D determinants of the H-2d haplotype, and expanded in tissue culture in the presence of interleukin 2, were capable of rapidly killing lethally irradiated BALB/c recipients when injected intravenously. Mice given 10(6), 10(7) and 10(8) such T cells survived 10.5, 8.5 and 0.5 days respectively. Mice given irradiation only survived 10.5 days. Mice given 10(8) B6 T cells activated against all determinants of a third party haplotype (H-2k) survived 8.5 days. Respiratory distress developed within 3 hr of injection in mice given 10(8) T cells activated against the H-2 alloantigens of the recipient haplotype, and at autopsy their lungs showed pulmonary congestion, focal obliteration of the alveolar space and thickening of alveolar interstitial tissue with fibrin, red cell and a mononuclear cell infiltrate. These findings may have relevance to the use of cellular immunotherapy.

Animals↗
PubMed1981

Interleukin 2 production by alloantigen (H-2) activated T cells.

H-2 alloantigen-activated T cells release Interleukin 2 in response to a secondary stimulus by either Concanavalin A or alloantigen. No detectable lymphokine is released in the absence of secondary stimulation and, in the case of alloantigen restimulation, lymphokine release is antigen-specific. Once formed, however, the lymphokine shows no antigen specificity in its action. Like the precursor of the cytotoxic T cell, the precursor of the Interleukin 2-producing T cell requires two signals for its activation; alloantigen and a source of costimulator activity. Once activated, T cells will release lymphokine in response to alloantigen alone.

Animals↗
PubMed1981

Interleukin 2 production by both Ly2+ and Ly2- T-cell subsets.

Homogeneous T-cell populations produced by activating lymphocytes to I-, K-, or K+ D- region-encoded determinants of the mouse H-2 complex release interleukin 2 when restimulated by concanavalin A. Contrary to earlier reports on the cellular origin of the lymphokine, we find that interleukin 2 production can be either Ly2+ or Ly2- T-cell-dependent.

Animals↗
PubMed1981

Inhibition of T-cell activity by cyclosporin A.

Cyclosporin A (CyA) inhibits early events in the T-cell response. It strongly suppresses the activation of naive T cells by IL1 or IL2 and alloantigen. CyA exerts a selective effect on activated T cells. It inhibits the ability of these cells to release IL2 in response to antigen or mitogen restimulation, at concentration that have no effect on the ability of these same cell populations to respond to IL2 by proliferation. The specific effects of CyA are not limited to T cells, however, and this drug will inhibit IL1 production by lipopolysaccharide W-stimulated PU5-IR cells.

Animals↗
PubMed1980

Reversal of diabetes by allogenic islet transplantation without immunosuppression.

Streptozotocin-induced diabetes is temporarily reversed following the allo-transplantation of BALB/c (H-2d) islet tissue to normal CBA (H-2k) recipients, but by 2-4 week post-transplantation these animals return to their initial diabetic condition. Organ culture of allogeneic islet tissue in 95% O2 and 5% CO2 for 7 days prior to transplantation reduces the immunogenicity of the tissue, and cultured allografts give prolonged (greater than 110 days) reversal of diabetes in normal allogeneic recipients. The non-fasting blood sugar level remains in or very close to the normal range, urine glucose output is one to two orders of magnitude less than that of diabetic control animals and allografted animals regain their pre-morbid body weight within 60 days of transplantation. Surgical removal of the allograft results in a rapid return of the animal to the initial diabetic condition.

Animals↗
PubMed1980

An improved assay for interleukin 2 (lymphocyte growth factor) produced by mitogen-activated lymphocytes.

The continued proliferation of activated T cells requires the presence of a lymphocyte growth factor in the culture medium. This study describes a rapid, highly reproducible assay to quantitatively measure levels of this lymphokine. The use of Concanavalin-A blast cells given this assay a high degree of flexibility and convenience. It is shown that the lymphokine measured is interleukin 2. The presence of an inhibitor in the supernatant of mitogen activated lymphocytes and the species specificity of the factor are demonstrated.

Animals↗
PubMed1980

Cellular requirements for production and release of the lymphocyte costimulator.

The lymphocyte costimulator (CoS) is a lymphokine required for the activation of T cell responses to H-2 alloantigens or mitogen, CoS activity is found in the supernatant medium of Concanavalin A (Con A) stimulated spleen cells, In this paper we investigate the cellular requirements for CoS production by Con A-activated mouse spleen cells. Maximal lymphokine production in response to Con A depends on a co-operative interaction between T cells and a nylon wool-adherent cell present in the spleen of nude mice. T cells appear to be the major producers of CoS activity, doing so only in response to an initial inductive stimulus supplied by nude spleen cells. The inductive stimulus is found as a soluble factor in the supernatant of Con A-activated spleen cells, and can also be provided by stimulatory (S+), but not by non-stimulatory (S-), tumour cells H-2 identical with the responding T cells. The activation of lymphokine-producing T cells is thus a two-signal process, requiring both mitogen and an additional inductive signal. Once activated, homogeneous populations of T cells will release lymphokine in response to mitogen alone.

Animals↗
PubMed1980

Cellular changes in cultured mouse thyroid glands and islets of Langerhans.

Islets of Langerhans cultured 7 days in vitro no longer contained any capillary endothelial cells, but their endocrine cells remained ultrastructurally normal up to 14 days. Vascular endothelial cells were also lost from cultured thyroid lobes, but more slowly. Thyroid endothelium was readily identified after 7 days of culture, although many cells appeared to be degenerating, and a few degenerating endothelial cells were still present after 14 days in culture. Erythrocytes and leukocytes in the lumina of thyroid vessels were observed to degenerate at about the same rate as the endothelial cells, while those in islet capillary lumina were largely washed out during isolation of the islets. Thyroid lymphatic endothelium and the numerous adipose cells present in this tissue also degenerated during the culture period. Follicle epithelial cells remained viable throughout the culture period, but the number of colloid droplets and endocytic vesicles they contained was markedly, decreased. Thyroid fibroblasts remained viable and appeared to enlarge and accumulate dense granules during culture. These cells were a prominent feature of thyroid lobes after 14 days of culture. Parathyroid tissue associated with the thyroid lobes showed viable endocrine cells but a loss of vascular endothelium after 14 days in culture. The loss of blood leukocytes and vascular endothelial cells in probably the major factor in the altered behavior of thyroid and islet allografts after culture in vitro.

Animals↗
PubMed1980

H-2 complex and Ia antigens on cells dissociated from mouse thyroid glands and islets of Langerhans.

Mouse thyroid tissue was dissociated with collagenase, fixed in periodate-lysine-paraformaldehyde (PLP), and further dissociated with EDTA and trypsin to yield cell suspensions containing mainly follicle epithelial cells and vascular endothelial cells. H-2 complex antigens were detected on the vascular endothelial cells at about the same high density as on peritoneal macrophages, and at a lower concentration on the laterobasal membranes of follicle epithelial cells. Neither of these cell types expressed detectable Ia antigens, but a minor cell type was presented that showed dense expression of Ia antigens. This cell type was probably a passenger leukocyte. It showed ultrastructural characteristics closely resembling those of spleen dendritic cells, which are known to express Ia antigens and to be potent stimulator cells in mixed lymphocyte culture. Dissociation of thyroid glands that had been cultured in vitro for 14 days yielded only follicle epithelium, and these cells showed the same labeling density of H-2 complex antigens as on uncultured cells. Dissociation of islets of Langerhans yielded capillary endothelial cells and beta cells, neither of which expressed detectable Ia antigens. The labeling results are discussed in relation to the cellular changes that occur during culture in vitro and the altered behavior of cultured allografts.

Animals↗
PubMed1980

Modulation of tissue immunogenicity by organ culture. Comparison of adult islets and fetal pancreas.

Uncultured mouse islet allografts (BALB/c to CBA) are rejected 2 to 4 weeks after transplantation. Allografts, cultured in 95% O2 and 5% CO2 for 7 days before transplantation, show no sign of rejection up to 3 months post-transplantation. However, the cultured allografts are rejected if the CBA recipient is given an i.v. injection of 10(5) peritoneal cells at the time of transplantation. Organ culture of BALB/c fetal pancreas (16 to 17 days gestation) under the same conditions failed to prevent allograft rejection. The immunogenicity of fetal pancreas is reduced if this tissue is cultured in 95% O2 and 5% CO2 for 17 days before transplantation.

Animals↗