Allograft immunity

Shepherd, D. et. al., Anti-CD40 Treatment of 2,3,7,8-tetrachlorodibenzo-p-dioxin-exposed C57B1/6 mice induces activation of antigen presenting cells yet fails to overcome TCDD-induced suppression of allograft immunity, Toxicol. Appl. Pharmacol., 170, 10, 2001. 

After tissue transplantation, the severity and the period of rejection depend on the tissue type, and this process involves the specificity and memory components of the immune response. Avrion Mitchison in the 1950s observed that allograft immunity could be transferred by the components of the cellular immune response, and antibodies present in the serum that were part of the humoral response were not associated with this process. Future studies delineated the role of T lymphocytes in the allograft rejection process, and the role of both CD4+ and CD8+ cells was established. 

O T cells are the chief components initiating the immune response against the allograft. The activity of T cells is mediated largely through the synthesis and release of interleukin-2 (IL-2). 

Tolerance is the process that allows organ-specific antigens to be accepted as self.2,6 This would mean that the immune system would cease to respond to the allograft, and immunosuppressive medications would not be necessary. Immune tolerance has not been accomplished successfully in humans.2,6... 

APCs, antigen-producing cells MMF, mycophenolate mofetil OKT-3, muronomab-CD3. (Adapted from Mueller XM. Drug immunosuppressive therapy for adult heart transplantation I. Immune response to allograft and mechanism of action of immunosuppressants. Ann Thorac Surg 2004 77 354-362, with permission.)... 

Allograft Tissue or organ transplanted from a donor of the same species but different genetic makeup the recipient s immune system must be suppressed to prevent rejection of the allograft (graft). 

Allograft rejection is thought to be primarily the result of a T helper 1 (Thl)-type immune response. Thl-like T cells often express CXCR3 and CCR5. T... 

Nelson PJ, Krensky AM. Chemokines, chemokine receptors, and allograft rejection. Immunity 2001 14 377-386. 

Balgia, P. et al., CTLA4Ig prolongs allograft survival while suppressing cell-mediated immunity, Transplantation, 58, 1082, 1994. 

Kapp JA, Honjo K, Kapp LM, Xu X, Cozier A, Bucy RP TCR transgenic CD8+ T cells activated in the presence of TGF-fi express FoxP3 and mediate hnked suppression of primary immune responses and cardiac allograft rejection. Int Immunol 2006 18 1549-1562. 

Clinical pharmacology Basiliximab is a chimeric (mouse/human) interleukin-2 receptor antagonist. It is directed against the interleukin-2 receptor-alpha chain (CD25) on activated T-lymphocytes, and is a potent inhibitor of interleukin-2-mediated activation of lymphocytes, a critical pathway in the cellular immune response involved in allograft rejection. Another anti-CD25 monoclonal antibody, dacUzumab (Zenapax), has the same indication as basiliximab. 

Mendola, J., Wright, J. R., Jr., and Lacy, P. (1989). Oxygen free-radical scavengers and immune destruction of murine islets in allograft rejection and multiple low-dose strep-tozocin-induced insulitis. Diabetes 38, 379-385. 

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