Ostracisme (sociologie)

L’ostracisme (ou rejet social) est une forme d'exclusion délibérée d’un individu d’une relation interpersonnelle ou d’une relation sociale. Cela inclut le rejet interpersonnel et le rejet sentimental. Un individu peut être rejeté, à cause d’une base individuelle, par un autre individu ou par un groupe entier de personnes. En outre, le rejet peut se manifester par des actes de harcèlement, d'intimidation ou par des actions physiques et/ou morales blessantes et/ou ridicules ou passives qui consisteront dans le fait d’ignorer une personne ou de lui infliger un type de « bizutage » silencieux. L’expérience du rejet est subjective pour l’individu qui le subit et peut être perçue lorsqu’il n’est pas réellement présent. Bien que les êtres humains aient une attitude sociale, certains niveaux de rejet restent inévitables durant une partie de la vie. Néanmoins, le rejet peut devenir problématique lorsqu’il est prolongé ou persistant, lorsque la relation est importante, ou lorsque l’individu e

A non-cleavable mutant of Fas ligand does not prevent neutrophilic destruction of islet transplants

Steinunn Baekkeskov Hanahan

Background. Fas ligand (FasL) mediates apoptosis of susceptible Fas-expressing lymphocytes, and may contribute to the maintenance of peripheral tolerance. In transplantation models, however, artificial expres- sion of FasL on cellular as well as islet transplants results in accelerated rejection by neutrophils. The mechanism of the neutrophilic response to FasL ex- pression is unknown. FasL, like other members of the tumor necrosis factor family, is cleaved to a soluble form by metalloproteases. We tested the hypothesis that soluble FasL (sFasL) was responsible for neutro- phil migration by creating a non-cleavable mutant of FasL. Methods. Three mutants of FasL with serial dele- tions in the putative proteolytic cleavage site of hu- man FasL were made using inverse polymerase chain reaction. The relative fractions of sFasL and mem- brane-bound FasL were assessed by Western blot and immunoprecipitation, as well as by cytotoxicity assay using Fas-expressing target cells. The fully non-cleav- able mutant was transduced into murine islets as well as myoblasts and tumor cell lines, and tested in a mu- rine transplantation model. Results. Serial deletions in the putative metallopro- tease site of FasL resulted in a fully non-cleavable mutant of FasL (ncFasL). Expression of ncFasL in tu- mor lines induced higher levels of apoptosis in Fas bearing targets than wild-type FasL. Transplantation of ncFasL-expressing islets under the kidney capsule of allogenic mice resulted in accelerated rejection identical to that seen with wild-type Fas ligand-expressing islets. Myoblasts and tumor cell lines express- ing ncFasL also induced neutrophil infiltration. Conclusions. Membrane-bound Fas ligand is fully ca- pable of inducing a neutrophilic response to trans- plants, suggesting an activation by Fas ligand of neu- trophil chemotactic factors.

Lippincott, Williams & Wilkins2000

Islet Transplantation in Mice Differing in the I and S Subregions of the H-2 Complex

Steinunn Baekkeskov Hanahan

Pancreatic islets from A.TH mice were transplanted into the spleen or streptozotocin (SZ)-diabetic A.TL mice. The two strains of mice are congenic inbred strains, differing only in the I and S subregions of the H-2 complex. The allogeneic islet grafts decreased blood glucose temporarily, but the islets were rejected after 21 ± 7 days (mean ± SD). The effect of skin presensitization was tested by giving both allogeneic and syngeneic skin grafts to each of a second set of A.TL mice before streptozotocin treatment and islet transplantation. The time course of rejection of the allogeneic islets in animals that received initial skin grafts was decreased to 8 ± 3 days. In both skin-presensitized and non-presensitized mice syngeneic islet grafts were able to restore normoglycaemia, even in animals that had previously rejected an islet allograft. These observations demonstrate that transplantation of pancreatic islet allografts across the I and S subregions of the H-2 complex is sufficient to induce rejection of the islets. The islet rejection was markedly accelerated by prior sensitization with allogeneic skin grafting. It is suggested that elements in allogeneic skin grafts serve as inducers of cytotoxic T-cell responses directed against gene products of the I and/or S subregions present on cells in the allogeneic islets.

Wiley-Blackwell1982

A non-cleavable mutant of Fas ligand does not prevent neutrophilic destruction of islet transplants

Steinunn Baekkeskov Hanahan

Lippincott, Williams & Wilkins2000

Adaptive rejection of unstable disturbances

A non-cleavable mutant of Fas ligand does not prevent neutrophilic destruction of islet transplants

Islet Transplantation in Mice Differing in the I and S Subregions of the H-2 Complex

Adaptive rejection of unstable disturbances

Islet Transplantation in Mice Differing in the I and S Subregions of the H-2 Complex

A non-cleavable mutant of Fas ligand does not prevent neutrophilic destruction of islet transplants