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T-cell regulation by CD28 and CTLA-4
M L Alegre1, K A Frauwirth, C B Thompson
1Department of Medicine, Section of Rheumatology and Committee in Immunology, Chicago, Illinois 60637, USA. malegre@midway.uchicago.edu
Nature Reviews. Immunology
|March 22, 2002
Summary
T lymphocyte activation requires T-cell receptor signaling and co-stimulatory signals. Integrating positive and negative signals, like those from CD28 and cytotoxic T-lymphocyte antigen 4 (CTLA-4), fine-tunes immune responses.
Area of Science:
- Immunology
- Cellular Biology
Background:
- T lymphocyte activation is a critical process in adaptive immunity.
- It is traditionally understood to require at least two signals: antigen recognition via the T-cell receptor (TCR) and engagement of co-stimulatory receptors.
Purpose of the Study:
- To elucidate the specific signaling roles of co-stimulatory receptors in T lymphocyte activation.
- To understand how inhibitory signals modulate the integration of co-stimulatory pathways.
Main Methods:
- Review of recent studies on T lymphocyte co-stimulation.
- Analysis of signaling networks involving CD28 and cytotoxic T-lymphocyte antigen 4 (CTLA-4).
Main Results:
- Co-stimulatory receptors, such as CD28, provide essential signals for T cell activation.
- Inhibitory signals, exemplified by cytotoxic T-lymphocyte antigen 4 (CTLA-4), counterbalance co-stimulatory pathways.
- The interplay between positive and negative co-stimulatory signals creates a complex regulatory network.
Conclusions:
- The integration of diverse co-stimulatory and inhibitory signals dictates the magnitude and outcome of immune responses.
- Understanding these complex signaling networks is crucial for modulating immune responses effectively.