Human Lymph Nodes Maintain TCF-1^hi Memory T Cells with High Functional Potential and Clonal Diversity throughout...

Area of Science:

• Immunology
• Cell Biology
• Translational Medicine

Background:

• Understanding human T cell responses in lymphoid organs is crucial for translating mouse model findings.
• Current knowledge of human T cell responses in lymphoid sites and their relation to peripheral blood is limited.

Purpose of the Study:

• To identify distinct differentiation and functional profiles of memory CD8+ T cells in human lymph nodes (LN) compared to other anatomical compartments.
• To characterize the transcriptional and functional attributes of LN memory CD8+ T cells.

Main Methods:

• Utilized a unique human tissue resource for comparative analysis of T cells from various anatomical sites within individual donors.
• Employed whole-transcriptome and high-dimensional cytometry by time-of-flight (CyTOF) profiling.

Main Results:

• Identified a subset of memory CD8+ T cells in human LN with distinct quiescence and self-renewal signatures, unlike those in blood, spleen, bone marrow, and lungs.
• LN memory CD8+ T cells express stem cell factors (TCF-1, LEF-1) and T follicular helper cell markers (CXCR5, CXCR4) with reduced effector molecules.
• These LN cells exhibit higher proliferation, greater TCR clonal diversity, and homology to mouse T cells responsive to checkpoint blockade immunotherapy.

Conclusions:

• Human LN harbor memory CD8+ T cells with significant expansion potential and diverse recognition capabilities.
• These LN memory T cells represent important targets for advancing immunotherapies.