Chapter category: Autoimmunity
CTLA-4 in Multiple Sclerosis
CTLA-4 in Autoimmune Disease
Edited by: Flemming PociotISBN: 1-58706-068-X
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Chapter authors:
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 control autoimmunity. This pathway is complex because the B7-1 and CD86 costimulatory molecules have dual specificities for CD28 and CTLA-4. B7-1 and CD86, provide the major costimulatory signal for augmenting and sustaining T cell immune responses via interaction with CD28.1 In contrast, engagement of B7 on antigen presenting cells (APCs) by CTLA-4 on T cells delivers signals that inhibit T cell responses.2,3 Thus, ligation of CTLA-4 has the opposite effect on T cells as ligation of CD28, although both receptors bind the same B7 molecules on APCs. The important immunoregulatory roles of the B7:CD28/CTLA-4 pathway prompted studies investigating how this pathway influences the initiation and progression of autoimmune diseases. As key regulators of T cell activation, B7:CD28 and B7:CTLA-4 interactions play important roles during the pathogenesis of autoimmune diseases. This chapter summarizes recent advances in our understanding of the role of the CD80/CD86:CD28/CTLA-4 pathway in the pathogenesis of autoimmune disease with emphasis on the role of CTLA-4 in regulating experimental autoimmune encephalomyelitis (EAE). EAE is a chronic inflammatory demyelinating disease of the central nervous system (CNS) and has been used as an animal model for human multiple sclerosis (MS). Disease susceptibility to EAE, diabetes, lupus, and autoimmune ovarian dysgenesis has been linked to the CD28/CTLA-4 locus.4-8 Genetic studies indicate that these pathways may contribute to the pathogenesis of human autoimmune diseases. We will focus on studies in EAE models which provide insights into how CTLA-4 may regulate the pathogenesis of EAE and have relevance to understanding the role of CTLA-4 in MS. The field is complicated by the multiple models of EAE in which different genetic strains of mice are immunized with various myelin antigens. However, we will emphasize common themes that have emerged from these studies.
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...
