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Related Experiment Videos

Dynamic programming of CD8+ T lymphocyte responses.

Marianne J B van Stipdonk1, Gijs Hardenberg, Martijn S Bijker

  • 1Division of Cellular Immunology, La Jolla Institute for Allergy and Immunology, San Diego, CA 92024, USA.

Nature Immunology
|March 18, 2003
PubMed
Summary
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Antigen stimulation duration dictates T cell response. Longer stimulation (20h) promotes robust CD8+ cytotoxic T lymphocyte (CTL) expansion and function, while shorter stimulation (4h) leads to abortive expansion. This highlights the importance of signal duration in T cell activation.

Area of Science:

  • Immunology
  • Cellular Biology
  • T cell immunology

Background:

  • Naive T cell activation, differentiation, and survival are initiated by antigen-presenting cells (APCs).
  • The duration of antigenic stimulation is a critical factor in T cell development, but its precise role in CD8+ cytotoxic T lymphocyte (CTL) functional maturation in vivo remains to be fully elucidated.

Purpose of the Study:

  • To investigate the impact of varying antigenic stimulation durations on the in vivo functional development of CD8+ CTLs.
  • To determine if temporal control of APC priming influences CTL clonal expansion, differentiation, and effector functions.

Main Methods:

  • Utilized an APC model allowing temporal control over antigen presentation to naive T cells.
  • Compared the responses of CD8+ CTLs subjected to a 4-hour versus a 20-hour antigenic stimulus.

Related Experiment Videos

  • Assessed clonal expansion, surface CD25 expression, and target tissue destruction mediated by CTLs.

    • Main Results:

    • CD8+ CTLs receiving a 4-hour stimulus exhibited limited clonal expansion and transient CD25 expression.
    • CD8+ CTLs exposed to a 20-hour stimulus demonstrated sustained CD25 up-regulation, extensive proliferation, and effective peripheral target tissue destruction.
    • Signal duration preceding the first cell division influences the decision between T cell activation and tolerance.

    Conclusions:

    • The duration of antigenic stimulation is a key determinant of CD8+ CTL functional outcomes.
    • Prolonged antigen exposure is essential for robust CTL expansion, differentiation, and effector function.
    • T cell activation thresholds are modulated by the integration of signal strength and duration during the initial priming phase.