Co-signal Molecules in T-Cell Activation

Historical Overview and Perspective
  • Miyuki AzumaEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1189)


The two-signal model of T-cell activation, proposed approximately four decades ago, has undergone various refinements while maintaining its principal doctrine. Since the discovery of CD28, a variety of co-signal molecules, including co-stimulatory and co-inhibitory receptors and ligands, have been identified. These molecules fine-tune various immune responses both in the primary or secondary lymphoid tissues and in the peripheral tissues. Most co-signal receptors are expressed and induced on T cells during distinct stages (naïve/resting, activating, memory, and exhausting). These co-signaling pathways play critical and diverse roles in maintaining T-cell tolerance and eliciting T-cell immune responses in health and disease. This introductory chapter provides a historical overview of the key findings that have led to our current view of T-cell co-stimulation.


Co-signals Co-stimulation Co-inhibition T-cell activation Two-signal model Tolerance 


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© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  1. 1.Department of Molecular Immunology, Graduate School of Medical and Dental SciencesTokyo Medical and Dental UniversityTokyoJapan

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