Chapter category: Autoimmunity
CTLA-4 in Systemic Lupus Erythematosus
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 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 responses and pathologic autoimmune responses. Furthermore, characterization of these costimulation pathways has suggested a number of new approaches for directing more specific immunosuppressive therapy for chronic autoimmune diseases such as systemic lupus erythematosus (SLE). Many experiments have now established the validity the two-signal hypothesis of Bretscher and Cohn.1 These studies have established that the first signal, provided by antigen specific stimulation of the T cell antigen receptor, is a necessary, but insufficient stimulus for maximal T cell activation and subsequent effector function. T cell activation, as manifested by IL-2 production and T cell proliferation, further requires a second, or costimulatory signal.2,3 A variety of specific interactions between T cells and antigen presenting cells (APC), or other accessory cells, can provide this second signal. However, the interaction between CD28 expressed on T cells and B7 molecules expressed on antigen presenting cells and activated B cells appears to provide the major costimulatory signal to T cells in a wide variety of adaptive immune responses.4 CD28 is constitutively expressed on the majority of T cells,5 while its ligands are expressed on the surface of activated, but not resting APC.6 Three B7 ligands have been described on activated human B lymphocytes; B7-1 (CD80), B7-2 (CD86) and B7-3, and two ligands, mB7-1 and mB7-2 have been identified of mouse B cells. Studies of CD28-deficient mice suggest that CD28 is the predominant receptor responsible for B7-dependent T cell activation.7 More recently, an inducible costimulatory molecule called ICOS that is structurally related to CD28, along with its ligand B7h, that is also homologous to other B7 molecules, have been described.8-10 These costimulatory molecules may deliver both complementary and unique costimulatory signals to T cells.11,12
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...
