GITR differentially affects lung effector T cell subpopulations during influenza virus infection

Area of Science:

• Immunology
• Cellular Biology
• Infectious Disease

Background:

• Tissue-resident memory T cells (Trm) are crucial for local immunity against reinfection.
• Trm accumulation relies on post-priming signals, including those from Glucocorticoid-induced TNFR-related protein (GITR; TNFRSF18).
• GITR signaling is vital for Trm formation during influenza virus infection.

Purpose of the Study:

• To investigate the differential effects of GITR signaling on distinct effector T cell subsets with varying memory potentials.
• To understand how GITR influences the accumulation and differentiation of CD4+ and CD8+ T cells.

Main Methods:

• Analysis of effector CD4+ T cell subsets based on Lymphocyte Antigen 6C (Ly6C) expression.
• Categorization of effector CD8+ T cells using Ly6C and CX3C chemokine Receptor 1 (CX3CR1) expression.
• Assessment of GITR's impact on T cell subset accumulation and surface marker expression (CXCR6, CD127) in vivo.

Main Results:

• GITR similarly affected the accumulation of both Ly6C-expressing CD4+ T cell subsets.
• GITR enhanced the accumulation of all CD8+ T cell subsets, with a greater effect on the less differentiated Ly6Clo CX3CR1lo subset.
• GITR selectively upregulated CXCR6 on less differentiated CD8+ T cells and CD127 on Ly6C-expressing CD4+ T cells.

Conclusions:

• GITR signaling contributes to the accumulation of both differentiated effector cells and memory precursors.
• GITR exhibits subset-specific effects on CD4+ and CD8+ T cells, influencing their differentiation and homing potential.
• These findings highlight GITR's complex role in shaping adaptive immunity at the tissue level.