Second signal for T lymphocyte activation: multiple targets for pharmacological modulation

Area of Science:

• Immunology
• Cellular Biology
• Drug Discovery

Background:

• T cell activation necessitates two signals: antigen recognition via the T cell receptor and co-stimulatory signals from adhesion molecules or cytokines.
• Immunomodulators can influence T cell responses by affecting these signals or later stages like cytokine production and receptor expression.

Purpose of the Study:

• To develop and validate an in vitro model for evaluating immunomodulators targeting the second signal of T cell activation.
• To assess the capacity of compounds to enhance adhesion molecule expression and monocyte cytokine synthesis, impacting T cell proliferation.

Main Methods:

• Devised an accessory cell depletion and reconstitution model for in vitro T cell activation studies.
• Evaluated compounds for their ability to modulate surface adhesion molecule expression and induce monocyte cytokine production.
• Assessed the impact of these modulations on T cell proliferation.

Main Results:

• The model successfully allowed for the assessment of immunomodulator activity on key components of the second signal.
• Compounds' effects on adhesion molecule expression and cytokine synthesis were correlated with their impact on T cell proliferation.

Conclusions:

• The developed accessory cell depletion and reconstitution model is effective for in vitro evaluation of immunomodulators.
• This model provides a framework for understanding how compounds influence T cell activation via the second signal, aiding in the development of novel immunotherapies.