Role Of Antibodies In Rejection Research Articles

Fate of alphaGal +/+ pancreatic islet grafts after transplantation into alphaGal knockout mice.

Important phylogenetic differences between pig and human tissues prevent xenotransplantation from becoming a clinically feasible option. Humans lack the galactose-alpha1,3-galactose (alphaGal) epitope on endothelial cell surfaces and therefore have preformed anti-alphaGal antibodies. The role of these antibodies in rejection of non-vascular xenografts remains controversial. This study investigated the role of anti-alphaGal antibodies in rejection of non-vascularized alphaGal+/+ grafts in alphaGal -/- mice. alphaGal +/+ and alphaGal -/- pancreatic islets were transplanted under the renal capsule of streptozotocin-induced diabetic (1) alphaGal -/- mice and (2) alphaGal +/+ mice. alphaGal -/- recepients were immunized with rabbit red blood cell membranes (RRBCs) to produce elevated anti-alphaGal antibody levels. Six of the 18 alphaGal -/- mice rejected the alphaGal +/+ grafts within 68 days whereas indefinite graft survival was achieved in the control groups. Animals with surviving islet grafts were challenged with alphaGal +/+ skin grafts. Although all alphaGal +/+ skin grafts were rejected within 58 days, the islet grafts remained intact. This observation correlated with the level of alphaGal expression (which was very low on islets compared to skin) rather than the actual titre of anti-alphaGal antibody. The results suggest that the level of alphaGal expression plays an important role in graft survival. Therefore, its removal is important in the development of a pig islet donor for future clinical therapy.

Role of antibodies in rejection

Recent evidence suggests that antibody plays a role in the pathogenesis of both acute rejection and accelerated coronary artery disease following human cardiac transplantation. There is strong evidence that posttransplant monitoring identifies patients at risk of developing transplant-associated coronary artery disease. That antibody is either essential for or influences the nature of the vascular lesion is supported by experimental models of cardiac graft vasculopathy. One of the major concerns in this area is that the specificities of antibodies (formed in patients) remain poorly defined. Major histocompatibility and non–major histocompatibility target antigens have been described. Traditionally, cytotoxic antibodies have been detected, but newer methods of detecting noncytotoxic antibodies and use of endothelial cells as targets should expand and clarify the range of antibodies being produced. The mechanism whereby antibody causes vascular lesions is not understood but almost certainly involves activation of donor endothelial cells. Indirect presentation of graft antigens (including non-HLA or minor antigens) and epitope spreading drive chronic rejection; such an expansion of the immune response probably includes antibody production against many different HLA and non-HLA antigens.

Cysticercosis: cellular immune responses during primary and secondary infection

Immune reactions to cysticercosis have been extensively studied in mice. The lack of significant lymphocyte infiltration into the livers of infected mice and the obvious role of antibodies in rejection has led to the general conclusion that cellular reactions do not play a role in protection against this disease. In contrast, the present study examining the immune response to cestode infections in a large animal model (sheep) revealed the presence of a massive and highly organized cellular infiltration in the livers after a secondary Taenia hydatigena infection. The majority of the infiltrating lymphocytes were of the CD4+ phenotype with much fewer CD8+ cells present. While most gamma delta-TCR+ cells in peripheral blood are SBU-T19+, the majority of gamma delta-TCR+ lymphocytes in the liver lesions are SBU-T19- suggesting selective migration of these cells into the lesions. In contrast to the diffuse distribution of T cells in the lesions, B cells were present as distinct aggregates. In primary T. hydatigena infections, host class I and class II MHC antigens were shown, for the first time in cestode infections, to be absorbed onto the surface of the metacestode bladderwall indicating their possible involvement in parasite survival. No immune reactions were observed close to the parasite although lymphocytes and eosinophils were infiltrating the adjacent portal tract areas. Most lymphocytes in both primary and secondary infections were positive for MHC class II antigens suggesting selective recruitment of activated cells to the site of infection. Significant changes in relative and absolute numbers of lymphocyte subpopulations were also observed in the draining hepatic lymph nodes dominated by a massive increase of B cells. In contrast, at the peak of local cellular infiltration, no changes in lymphocyte subpopulations were observed in peripheral blood showing the limited usefulness of this compartment in studying cellular changes in localized infections. The vigorous cellular response observed in the livers of sheep contrasts sharply with the lack of lymphocyte infiltration reported in mice indicating that small animal models may not be appropriate to study cellular responses to cysticercosis in large animals and man.