Compartmentalization of Total and Virus-Specific Tissue-Resident Memory CD8+ T Cells in Human Lymphoid Organs

Area of Science:

• Immunology
• Virology
• Cell Biology

Background:

• Severe immune suppression can lead to reactivation of chronic viral infections, including Epstein Barr virus (EBV) and Cytomegalovirus (CMV).
• The specific roles of different memory T cell subsets in protective immunity against these viruses are not well understood.

Purpose of the Study:

• To investigate the compartmentalization of virus-specific, tissue-resident memory CD8+ T cells in human lymphoid organs.
• To define distinct subsets of memory CD8+ T cells and their anatomical localization within the spleen and tonsils.

Main Methods:

• Analysis of virus-specific CD8+ T cells in human spleen and tonsils.
• Phenotypic and transcriptional profiling of distinct T cell populations (CD69+CD103+ and CD69+CD103-).
• In vitro studies on the role of IL-15 in T cell retention.

Main Results:

• Identified two distinct populations of memory CD8+ T cells (CD69+CD103+ and CD69+CD103-) retained in spleen and tonsils.
• These populations exhibited unique phenotypes, transcriptional profiles, and anatomical distributions.
• EBV-specific CD8+ memory T cells preferentially localized to tonsils, acquiring a phenotype for retention at epithelial sites.
• Interleukin-15 (IL-15) was found to enhance T cell retention by down-regulating sphingosine-1-phosphate receptor and KLF2 expression.

Conclusions:

• Distinct subsets of resident memory CD8+ T cells are compartmentalized within human lymphoid organs.
• These specialized T cell populations likely contribute to long-term protective immunity against persistent viral infections like EBV.
• IL-15 plays a role in retaining CD8+ T cells within tissues, particularly in the tonsils.