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Lymphoid environment limits superantigen and antigen-induced T cell proliferation at high precursor frequency
A Attinger1, H R MacDonald, H Acha-Orbea
1Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne Epalinges, Switzerland.
European Journal of Immunology
|March 10, 2001
Summary
The lymphoid environment limits T cell proliferation when T cell frequencies are high. Dendritic cells likely restrict T cell expansion by limiting antigen-presenting cell availability, impacting T cell priming.
Area of Science:
- Immunology
- Cell Biology
- T cell activation
Background:
- Superantigen challenge can lead to a significant proportion of T cells remaining undivided.
- The frequency of antigen-reactive T cells can influence their proliferation and division within the lymphoid environment.
Purpose of the Study:
- To investigate how the frequency of superantigen-reactive T cells affects T cell proliferation in secondary lymphoid organs.
- To identify factors within the lymphoid environment that limit T cell proliferation.
Main Methods:
- Transfer of fluorescently labeled T cells into recipients at varying frequencies (1%, 15%, 30-100%).
- Monitoring T cell proliferation and the percentage of undivided cells.
- Confirmation using peptide antigens and T cell receptor (TCR)-transgenic mice.
- In vivo and in vitro experiments to assess the role of dendritic cells.
Main Results:
- At low frequencies, reactive T cells proliferated maximally.
- At intermediate frequencies, a proportion of T cells did not enter cell cycle, and overall division decreased.
- Higher frequencies did not increase undivided cells but further reduced divisions.
- Dendritic cells were identified as likely regulators of T cell proliferation.
Conclusions:
- The availability of antigen-presenting cells (APCs) in the lymphoid environment quantitatively limits T cell priming.
- Lymphoid environment constraints on T cell proliferation are dependent on the frequency of reactive T cells.