Chapter category: Autoimmunity
CTLA-4: Its Role in Transplant Tolerance and Rejection
CTLA-4 in Autoimmune Disease
Edited by: Flemming PociotISBN: 1-58706-068-X
» Get more information about this book at landesbioscience.com «
Chapter authors:
David M. Rothstein and Fadi G. Lakkis
Transplantation is the treatment of choice for end-stage heart, kidney, liver, and pancre atic islet disease. Current strategies require life-long immunosuppression in attempts to inhibit the alloimmune response and prevent acute and chronic rejection.Tolerance remains the holy grail for achieving permanent engraftment of transplanted organs while avoiding the attendant risks of chronic immunosuppression such as infection and malignancy. Allograft rejection is a T cell dependent process. The realization that T cell activation requires signaling through both the T cell receptor for antigen (TCR) and costimulatory molecules, such as CD28, provided new insight into the T cell response. Moreover, the realization that interference with such pathways could alter or block the immune response altogether, provided new strategies for the induction of long-term engraftment through the targeting of T cell signaling molecules. Specifically, interference with the interaction of CD28 with its B7 ligand on antigen presenting cells (APCs) during TCR engagement can induce anergy in T cell clones and prolong allograft survival in a number of animal models. The identification of CTLA-4 as a second ligand for B7 that has potent inhibitory activity in T cells, provided new insight into the nature of tolerance and the balance between positive and negative regulatory signals that regulate T cell activation. Understanding the role of CTLA-4 in allograft rejection and tolerance will assist in designing therapeutic strategies to manipulate positive and negative immunoregulatory pathways.
Additional chapters from this book:
CTLA-4: Its Role in Transplant Tolerance and Rejection
David M. Rothstein and Fadi G. Lakkis
Transplantation is the treatment of choice for end-stage heart, kidney, liver, and pancre atic islet disease. Current strategies require life-long immunosuppression in attempts to inhibit the alloim...
CTLA-4 in Type 1 Diabetes Mellitus
Lorenza Nisticò, Isabella Cascino, Raffaella Buzzetti and Paolo Pozzilli
The current etiological classification defines type 1 diabetes as a chronic hyperglycemia due to a cellular mediated immune destruction of the insulin-secreting pancreatic beta-cells. This disease i...
CTLA-4 in Addison’s Disease
Klaus Badenhoop
Addison’s disease is a rare autoimmune disorder of adrenal destruction leading to death if unrecognised and untreated. Usually non-surgical adrenal insufficiency is caused by either tuberculous gran...
CTLA-4 in Multiple Sclerosis
Rebecca J. Greenwald, Yvette Latchman and Arlene H. Sharpe
The B7:CD28/CTLA-4 pathway has a pivotal role in regulating T cell immune responses and manipulation of this key immunoregulatory pathway may lead to the development of therapeutic interventions to ...
CTLA-4 in Myasthenia Gravis
Ann Kari Lefvert
Myasthenia gravis (MG) is commonly regarded as the prototype for an organ specific antibody-mediated autoimmune disease. The disease is characterized by an immune response against the nicotinic acet...
CTLA-4 in Rheumatoid Arthritis
Peter P. Sfikakis and Stamatis-Nick Liossis
Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disease characterised by symmetric polyarthritis of the small joints of the hands and feet and the larger appendicular joints. The etiol...
CTLA-4 in Systemic Lupus Erythematosus
David I. Daikh and David Wofsy
The recent characterization of several costimulatory interactions between antigen presenting cells and T cells represents a major advance in our understanding of both normal adaptive immune response...
CTLA-4: Its Role in the Immune Response
Maria-Luisa Alegre and Thomas F. Gajewski
T lymphocytes are essential for host defense against many viral or parasitic infections, and also contribute to defense against tumors. In addition, T cells mediate rejection of transplanted organs,...
Autoimune Disorders—A Common Link?
Flemming Pociot
The immune system has evolved to protect multicellular organisms from pathogens. It is therefore perplexing that this system turns on the individual, in some cases precipitating catastrophic autoimm...
