PubMed Health⌕ Search

Biomedical subjects

G Selvaggi

Publications and source records attributed to G Selvaggi.

At least 55 records · Page 3Linked to original sources
PubMed1996

The role of the perforin and Fas pathways of cytotoxicity in skin graft rejection.

Cell-mediated cytotoxicity is believed to play an important role in the mechanisms of rejection following organ and tissue transplantation. We have investigated the role of the perforin and Fas pathways of cell-mediated cytotoxicity on the survival of xenogeneic, allogeneic and hemiallogeneic skin grafts. Wild type C57BL/6 (B6), perforin deficient C57BL/6 (B6 PKO) and Fas ligand deficient (B6 gld/gld) mice were grafted with xenogeneic Lewis rat skin grafts, or allogeneic B10.BR, class I disparate B6 bml, class II disparate B6 bm12, and Fas deficient allogeneic C3H lpr/lpr grafts. No significant difference was observed in the timing of rejection with B6 PKO mice as recipients when compared with normal B6 controls. All grafts were also rejected by B6 gld/gld recipients, but with a significantly delayed pattern of rejection, showing, therefore, that Fas, although not critical, may participate to the mechanisms of rejection. Neither perforin nor Fas, however, seem to be essential for rejection of a skin graft, and it is likely that alternative mechanisms assume an important role in the effector phase of rejection once these cell-cytotoxic pathways are abrogated.

Animals↗
PubMed1996

Liver transplantation without immunosuppression: future perspectives.

It has been hypothesized that a state of microchimerism in recipients of organ transplants may result in donor-specific tolerance to the graft. Numerous studies show that infusion of donor-derived bone marrow cells can, indeed, achieve systemic chimerism in the recipient and effectively prolong allograft survival. We have compared organ and patient survival in recipients of liver allografts alone (controls) or in combination with single or multiple infusions of donor bone marrow cells; recipients were infused either at day 0 (perioperatively) or at day 0 and 11 post-transplant. The incidence of rejection episodes and survival of the liver allograft were significantly reduced in recipients of two bone marrow infusions compared to controls; recipients of one infusion, conversely, experienced a higher number of rejection episodes when compared to controls, pointing to a possible sensitizing role of a single bone marrow infusion if administered perioperatively. Variables such as timing, number and composition of the bone marrow inocula still remain to be elucidated but may be of critical importance for the attainment of a state of donor-specific tolerance without the need for immunosuppressive therapy in recipients of organ allografts.

Animals↗
PubMed1995

The influence of donor specific vertebral body derived bone marrow cell infusion on canine islet allograft survival without irradiation conditioning of the recipient.

In recent studies in rodents, it was shown, that donor specific tolerance towards islet allografts without irradiation therapy of the recipient is induced by bone marrow cell infusion in combination with temporary immunosuppression. In the present study, the effect of donor specific bone marrow cell (DBMC) infusion at the time of intrahepatic islet allotransplantation without irradiation conditioning of the recipient was investigated in the canine model, paralleling ongoing clinical trials. It was observed, that unfractionated bone marrow cells given simultaneous to islet allografts led to higher frequencies of rejection periods and decreased islet allograft survival, when administered to recipients immunosuppressed with Cyclosporine A only. In contrast, an additional short inductive treatment of the recipient with an anti-dog-T-lymphocyte monoclonal antibody (5G2) abrogated the enhanced immunogenicity of the unfractionated bone marrow preparation, prolonging islet allograft survival with no rejection episodes observed during the immunosuppressive treatment with Cyclosporine. The composition of bone marrow cells might have contributed to the higher immunogenicity, since the percentage of MHC-class II antigen bearing cells is similar to man, but significantly higher than compared to rodents. It is therefore suggested, that further studies should encompass both timing of bone marrow cell infusion, appropriate immunosuppression and strategies to functionally inactivate mature MHC-class-II positive cells prior to DBMC infusion.

Animals↗