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Related Experiment Videos

T-cell tolerance or function is determined by combinatorial costimulatory signals.

Roza Nurieva1, Sunil Thomas, Thang Nguyen

  • 1Department of Immunology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

The EMBO Journal
|May 26, 2006
PubMed
Summary

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T-cell activation and function depend on costimulatory signals. Blocking both CD28 and ICOS pathways induced T-cell tolerance, highlighting the critical role of these molecules in immune responses.

Area of Science:

  • Immunology
  • Cellular Biology
  • Molecular Medicine

Background:

  • T lymphocytes are crucial for adaptive immunity, differentiating into effector cells upon activation.
  • CD28 is a primary costimulatory receptor for T-cell activation, but its absence doesn't fully abolish effector function.
  • Numerous costimulatory molecules on antigen-presenting cells regulate T-cell activation, influencing immune outcomes.

Purpose of the Study:

  • To elucidate the molecular mechanisms governing T-cell function versus tolerance.
  • To investigate the combined roles of positive and negative costimulatory molecules in T-cell differentiation.
  • To identify critical pathways that dictate whether T cells become functional or tolerant.

Main Methods:

  • Activation of antigen-specific naive CD4 and CD8 T cells under varying costimulatory conditions.

Related Experiment Videos

  • Assessment of T-cell effector function, anergy, and signal transduction defects.
  • Evaluation of effector-specific transcription factor expression.
  • Inhibition of negative costimulatory molecules (PD-1, B7-H3, B7S1) to assess T-cell restoration.

    • Main Results:

    • Complete impairment of T-cell effector function occurred only when both CD28 and ICOS pathways were absent during activation.
    • T cells activated without CD28 and ICOS exhibited anergy, defective T-cell receptor signaling, and lacked effector transcription factors.
    • Inhibition of negative costimulatory molecules like PD-1, B7-H3, or B7S1 partially restored T-cell proliferation and function.

    Conclusions:

    • T-cell function or tolerance is precisely controlled by the balance of costimulatory signals.
    • The absence of key costimulatory pathways, alongside the action of negative regulators, is essential for inducing T-cell tolerance.
    • Understanding these costimulatory networks is vital for manipulating T-cell responses in immunotherapy and autoimmune diseases.