Regulation of T-cell activation by CD28 and CTLA-4

被引:1
|
作者
Nagel, T [1 ]
Kalden, JR [1 ]
Manger, B [1 ]
机构
[1] Univ Erlangen Nurnberg, Med Klin 3, D-91054 Erlangen, Germany
关键词
immunomodulation; T lymphocytes; costimulation; CD28; CTLA-4; CTLA-4Ig;
D O I
10.1007/BF03042674
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
T cell response: T lymphocytes play a key role in the coordination of the immune response. T helper cells contribute primarily by means of cytokine release, whereas cytotoxic T cells eliminate cells bearing antigens recognized as foreign. Through its T cell receptor each T cell can recognize a specific peptide antigen, which is presented in the context of the major histocompatibility complex (MHC) to T helper cells by specialized antigen-presenting cells or to cytotoxic T cells by nearly all body cells. Upon contact with its specific antigen, the T cell receptor transduces an activation signal into the T cell, leading to proliferation, cytokine production, or efficient cytotoxicity. Costimulation: However, a second costimulatory signal is necessary to achieve complete activation. This can be provided by the accessory T cell molecule CD28 upon binding to its respective ligands B7-1 (CD80) or B7-2 (CD86). The same ligands bind to CTLA-4 (CD152), a receptor expressed at the surface of T cells previously activated for 2 to 3 days and capable of downregulating activation. Immunosuppression by CTLA-4Ig: A genetically engineered soluble fusion protein containing the extracellular domain of CTL-4 and the Fc portion of an immunoglobulin heavy chain (CTLA-4Ig) prevents the interaction of CD28 and CTLA-4 with their B7 ligands, the subsequent activation T cells and thereby eliminates or reduces unfavorable immune system activation in transplant rejection or autoimmunity. Conclusion: The importance of the regulatory system comprising CD28, CTLA-4 and the B7 molecules and its modulation by CTLA-4Ig has been demonstrated in a substantial number of animal models in recent years and hods promise as a novel approach for therapeutic immunomodulation in humans .
引用
收藏
页码:592 / 597
页数:6
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