T cell: Lecture 5

Type I IFN

• Potent antiviral effects, activated by PRR activation
• Important anti-viral cytokines, inhibit or slow viral replication by intracellular signaling

CD4+ T Cell Subtypes

• TH1 responses: involved in response to infections by viruses and intracellular pathogens
• TH2 responses: involved in response to parasites, other extracellular pathogens, and allergy
• TH17 responses: involved in response to infections by extracellular bacteria and fungi, and autoimmunity
• TFH responses: involved in activating B cells in the lymph node

Cross-Regulation of T Cell Subtypes

• IL-4 inhibits TH1 differentiation, while IFN-gamma inhibits TH2 differentiation
• IL-4 can bind to receptors on naive CD4+ T cells, preventing differentiation into TH1
• IL-4 or IFN-gamma can inhibit TH17 differentiation

Master Transcriptional Regulators

• T-Bet: commits T cells to TH1 subset, inhibits IL-4/5 and GATA expression, suppressing TH2 pathway gene expression
• GATA3: inhibits expression of T-Bet and IFN-gamma, suppressing TH1 pathway gene expression

TH17/TREG Decision Point

• TGF-β is a key cytokine for differentiation of both TH17 and TREG subsets
• IL-6 is the "switch," inducing TH17 subset differentiation instead of TREG

Homing of T Cells

• Effector T cells express molecules that target specific tissues (e.g., skin vs gut), depending on the site of infection
• Different cell surface molecules are expressed by naive vs effector T cells, as they travel to different locations in the body

Cytokine Patterns and Functions

• Effector cytokine patterns are tied to function
• Cytokines and master transcriptional regulators regulate the expression of different T cell subsets
• The addition of different cytokines can switch the induction of one T cell subset over another

Type II IFN

• Role in immune response against intracellular pathogens
• IFN-gamma is the only Type II IFN, secreted by CTLs, increases MHC class I expression on neighboring cells, and activates macrophages