Choosing between immunity and tolerance after transplantation

Transplantation of MHC disparate solid organ leads to activation of both innate and adaptive immune responses. These immune responses include both effector and regulatory limbs. Lymphodepletion and IL-2 blockade may control the acute alloimmune response in humans but may also limit the regulatory arm. Numerous cytokines involved in rejection appear to be critical for tolerance. TLRs, complement engagement can facilitate suppressive responses as well as effector responses. Facilitating antigen-specific tolerance while enabling robust immunity may require ex vivo manipulation of the immune system rather than relying on in vivo perturbations of the homeostatic process.     

An influence of diet on transplantation immunity.

It was discovered by chance that mice raised under otherwise entirely conventional conditions of husbandry but fed upon autoclaved diet (diet A) had stronger cell-mediated immune reactions than those of mice raised under the same conditions but with an unmodified diet (diet B) : skin allografts were rejected more quickly, transplantation tolerance was more difficult to procure and fibrosarcomas induced by the injection of methylcholanthrene (MCA) arose more slowly and less often. Analysis showed that these findings could be explained at least in part by the discovery of Mertin & Hunt (1976, p. 928) that a partial deprivation of polyinsaturated fatty acids led to an intensification of cell-mediated immunity; on the other hand, experiments with dietary mixtures made it seem unlikely that this was the whole explanation and pointed towards some positive immunopotentiation by an ingredient of autoclaved diet. This, it was proposed, might be a compound of unknown composition resulting from the interaction of vitamin A with other dietary constituents. This interpretation was not supported by direct evidence but by confirming that retinol derivatives, especially retinyl acetate, could exercise an immunopotentiation of the kind and degree under investigation: retinyl acetate could counteract the immunosuppressive action of linoleic acid, though retinyl methyl ether was ineffective. Although retinyl derivatives may protect against MCA tumours by impeding its metabolic conversion to an oncogenic form, the effects of an autoclaved diet upon skin allograft survival, the induction of tolerance and the formation of tumours is probably mediated through an immunological mechanism.     

Humoral factors of transplantation immunity in carp]

The levels of isohemagglutinins, isohemolysins, heterohemagglutinins and lysozyme in blood serum of one and half year old carps have been fixed after scales transplantation. Since three weeks after grafting isohemagglutinins and isohemolysins were revealed in recipient fishes with the prevalence of 25% and 95% respectively. Intact carps from the same group were lack of these antibodies. Recipient and intact fishes did not differ reliably by heterohemagglutinins and lysozyme level in the blood serum. There was no correlation between destroyed allografts share and hemolysins titre of serum, so the double role of humoral antibodies in grafting immunity in carps can be assumed.     

TNFR2 signaling modulates immunity after allogeneic hematopoietic cell transplantation

Tumor necrosis factor-α (TNF-α) signaling through TNF receptor 2 (TNFR2) plays a complex immune regulatory role in allogeneic hematopoietic cell transplantation (HCT). TNF-α is rapidly released in the circulation after the conditioning regimen with chemotherapy and/or radiotherapy. It activates the function of donor alloreactive T cells and donor Natural Killer cells and promotes graft versus tumor effects. However, donor alloreactive T cells also attack host tissues and cause graft versus host disease (GVHD), a life-threatening complication of HCT. Indeed, anti-TNF-α therapy has been used to treat steroid-refractory GVHD. Recent studies have highlighted another role for TNFR2 signaling, as it enhances the function of immune cells with suppressive properties, in particular CD4⁺Foxp3⁺ regulatory T cells (Tregs). Various clinical trials are employing Treg-based treatments to prevent or treat GVHD. The present review will discuss the effects of TNFR2 signaling in the setting of allogeneic HCT, the implications for the use of anti-TNF-α therapy to treat GVHD and the clinical perspectives of strategies that specifically target this pathway.     

Nonspecific suppressive effect of Ehrlich tumor ascitic fluid on transplantation immunity]

The influence of syngeneic Ehrlich ascites tumour fluid on the survival of allogeneic skin allografts was investigated on CC57BR mice. A 3--4-day delay of the allograft rejection in mice injected with ascitic fluid was revealed. Preliminary transplantation of such allograft to mice with Ehrlich tumour produced no intensification of the immunodepressive action of the ascites fluid obtained from them. The data obtained indicated the preferential significance of the antigen-independent immunosuppressive factors of ascites tumour fluid in the suppression of the transplantation immunity in vivo.     

Ultrastructural changes in somatotropinocytes of the adenohypophysis during development of transplantation immunity

The authors conducted two series of experiments on 144 mice of BAL/c and C57B1 line. It was established that in autotransplantation submicroscopical changes developing in somatotropinocytes are typical of stressor situation and reflect various phases of general adaptation syndrome. An increase in the number of cells in the phase of active proteinic synthesis and degranulation is observed in allotransplantation in inductive phase of immunogenesis. Before rejection the number of cells in the phase of active proteinic synthesis is decreased, and in degranulation phase--is increased.