Cell Surface Signaling Molecules in the Control of Immune Responses: A Tide Model

Yuwen Zhu, Sheng Yao, Lieping Chen

Research output: Contribution to journalArticlepeer-review

104 Scopus citations


A large numbers of cell surface signaling molecules (CSSMs) have been molecularly identified and functionally characterized in recent years and, via these studies, our knowledge in the control of immune response has increased exponentially. Two major lines of evidence emerge. First, the majority of immune cells rely on one or few CSSMs to deliver a primary triggering signal to sense their environment, leading to initiation of an immune response. Second, both costimulatory CSSMs that promote the response, and coinhibitory CSSMs that inhibit the response, are required to control direction and magnitude of a given immune response. With such tight feedback, immune responses are tuned and returned to baseline. These findings extend well beyond our previous observation in the requirement for lymphocyte activation and argue a revisit of the traditional " two-signal model" for activation and tolerance of lymphocytes. Here we propose a " tide" model to accommodate and interpret current experimental findings.

Original languageEnglish (US)
Pages (from-to)466-478
Number of pages13
Issue number4
StatePublished - Apr 22 2011
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases
  • Immunology


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