Chapter category: Autoimmunity
Cytokines, Lymphocyte Homeostasis and Self Tolerance
Cytokines and Chemokines in Autoimmune Disease
Edited by: Pere SantamariaISBN: 0-306-47693-2
» Get more information about this book at landesbioscience.com «
Chapter authors:
Yiguang Chen and Youhai Chen
Cytokines play pivotal roles in maintaining lymphocyte homeostasis and self tolerance. Cytokines are required for activating and inactivating as well as deleting cells of the immune system during immune responses. Mutations in cytokine genes in humans and animals can lead to the breakdown of self tolerance and the development of autoimmune diseases. In this chapter, we will discuss the important roles of cytokines in lymphocyte homeostasis and self tolerance. Since many cytokines are involved, albeit to different degrees, in maintaining lymphocyte homeostasis, a complete review of all cytokines involved is beyond the scope of this chapter. Instead, we will focus on those cytokines whose gene mutations cause autoimmune problems. These include transforming growth factor–b, interleukin–10, interleukin–2, interferon–g and the tumor necrosis factor family of proteins.
Our immune system is capable of generating a diverse repertoire of lymphocyte antigen receptors with literally unlimited number of specificities. This is achieved through a random gene rearrangement process during lymphocyte development using a limited number of antigen receptor genes. Although such a strategy confers the immune system with the capacity to specifically recognize and respond to a vast range of foreign antigens, it also inevitably generates receptors capable of recognizing self antigens. Therefore, in order to prevent immune attack against self tissues, the immune system must eliminate or suppress lymphocytes that express self–reactive antigen receptors. On the other hand, although immune attacks against foreign antigens are required for eliminating infectious pathogens, they can also cause 'by–stander' injury to self tissues. Once the foreign antigens are removed, the immune response must be down–regulated and the activated effector cells be eliminated to ensure the homeostasis of the immune system and the wellbeing of the host. In the past decade, we have learned that the immune homeostasis and self tolerance are orchestrated by a highly complex and intricate network of membrane and secretory proteins. Prominent among these are antigen receptors, costimulatory molecules and cytokines. In this chapter, we will start with a general review of self tolerance and lymphocyte homeostasis. We will then focus on the roles of several key cytokines in maintaining lymphocyte homeostasis and self tolerance.
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