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K J Lafferty

Publications and source records attributed to K J Lafferty.

At least 91 records · Page 5Linked to original sources
PubMed1985

An analysis of tissue-specific transplantation phenomena in a minor histoincompatibility system.

Tissue-specific differences in immunogenicity were demonstrated following allotransplantation across the same minor histocompatibility barrier (BALB/c----DBA/2). In contrast to the high immunogenicity of fetal pancreas and skin, isolated islets, fetal proislets, and thyroid were weakly immunogenic. These tissue-specific effects were not related to the presence of tissue-specific antigens or the absence of recognizable minor alloantigens from the less immunogenic tissues. There was a strong correlation between tissues that were highly immunogenic and those that contained rich populations of donor leukocytes. The survival of fetal pancreas allografts was significantly improved by pretreating the donor tissue in high-oxygen organ culture and by the preparation of fetal proislets. Using other MHC-compatible strain combinations (B10.D2----BALB/c; BALB/c----B10.D2; C3H.SW----C57/10J) strain-specific effects were observed in the immunogenicity of thyroid allografts. In two of three strain combinations (B10.D2----BALB/c; BALB/c----B10.D2), pretreatment of the donor tissue with cyclophosphamide and organ culture prior to grafting significantly improved graft survival. These findings suggest that donor passenger leukocytes may play an important role in determining the immunogenicity of MHC-compatible allografts.

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↗
PubMed1985

Pancreatic islet transplantation--experimental experience and clinical potential.

New theoretic developments in transplantation biology indicate that it is possible to reduce the immunogenicity of a graft by removing antigen-presenting cells (leukocytes) from the tissue before grafting. Also becoming apparent is that cellular replacement therapy, the grafting of cells or clusters of cells, can be used to treat metabolic disorders such as type I diabetes mellitus. In the past, immune rejection has been a major problem and long-term patient immunosuppression is not warranted in patients with type I diabetes. Results of studies in animals show that under defined genetic conditions, mature islet tissue or immature fetal proislets may be transplanted across major histocompatibility barriers without a requirement for recipient immunosuppression. We are now ready to commence applying this technology clinically. These developments will initially be very experimental and limited in scope but should accelerate as data emerge from the initial trials.

Animals↗
PubMed1984

Syngeneic transplantation of cryopreserved fetal mouse proislets.

Proislets, derived from fetal mouse pancreata by collagenase digestion and subsequent organ culture, can be frozen to -196 degrees C and stored in a viable condition before successful syngeneic transplantation. Cryopreserved proislets are relatively undifferentiated morphologically, but continue to differentiate into mature islets after transplantation.

Animals↗
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.

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