In Vivo CD4⁺ T Cell Differentiation and Function: Revisiting the Th1/Th2 Paradigm

Area of Science:

• Immunology
• Molecular Biology
• Cell Biology

Background:

• The CD4+ T cell field was initially defined by master transcription factors and the Th1/Th2 paradigm.
• Recent advances highlight more intricate lineage-defining transcriptional networks governing CD4+ T cell differentiation in vivo.

Purpose of the Study:

• To review the layered fate decisions influencing CD4+ T cell differentiation in vivo.
• To explore how distinct signaling pathways shape CD4+ T cell effector functions.

Main Methods:

• Review of in vivo experimental systems and transcriptional network analyses.
• Examination of cytokine signaling from antigen-presenting cells and T cell receptor signals.

Main Results:

• Cytokine production by innate cells directs CD4+ T cell effector programs (Th1, Th2, Th17).
• T cell receptor signals differentiate clones into T follicular helper cells or tissue- } effector cells.
• These parallel pathways enhance effector programs and prevent disease.

Conclusions:

• CD4+ T cell differentiation is a multi-layered process involving complex transcriptional regulation.
• Distinct signaling pathways dictate whether CD4+ T cells support B cell antibody production or activate innate immune cells.
• This intricate regulation is essential for effective immunity and disease control.