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Differential retention of lymph-borne CD8 memory T cell subsets in the subcapsular sinus of resting and inflamed lymph nodes

Cellular & Molecular Immunology volume 18, pages 1317–1319 (2021)Cite this article

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Immunological memory represents the ability of specific immune cells to recall an encounter with a cognate pathogen. This results in an immediate response upon a second exposure to the same infectious agent. Thus, conventional memory T cells are generated after encountering specific foreign antigens. In contrast, a group of innate memory T cells develops without initial exposure to foreign antigen that specifically binds to a cognate T cell receptor.1 These naturally occurring memory-like T cells, also known as “virtual” memory T cells, are generated under steady-state conditions. They accumulate during aging in both humans and mice.2 By comparing the TCR repertoire of young and old mice, an early study identified age-dependent clonal expansion and age-related changes in CD8+ but not CD4+ T cells.3 Interestingly, more than 50% of CD62LhiCD44hi central memory T cells in the peripheral blood of aged naive mice have been suggested to represent virtual memory T cells based on their lower expression levels of CD49d.4 Infection studies in mice employing Listeria monocytogenes showed that both virtual memory T cells and conventional antigen-specific memory T cells were able to provide protection.5 However, in contrast to virtual memory T cells, conventional memory T cells produced fivefold higher levels of IFN-γ upon short-term in vitro TCR stimulation.5

The migration properties of different types of naive and memory immune cells have been studied for decades in animals using intravenous adoptive cell transfer. Although this approach is suited to studying the homing of immune cells from blood via specialized high endothelial vessels to lymph nodes (LNs), it does not provide any information regarding LN homing of cells that arrive via afferent lymphatics. To study the mechanisms permitting entry of lymph-derived cells and their subsequent intranodal positioning, we established an intralymphatic (IL) cell transfer technique in mice. With the help of microinjectors, immune cells are placed into the lymphatic vessels draining from the foot paw toward the popliteal LN.6 This approach revealed that in noninflamed LNs, lymph-derived naive CD4 T cells enter the paracortical T cell zone (TCZ) from the medullary sinuses, whereas activated T cells and dendritic cells enter the TCZ through the subcapsular sinus (SCS) floor at interfollicular areas (IFA). Both routes of homing rely on chemokine receptors, with CCR7 playing a prominent role.7 In addition, the atypical chemokine receptor ACKR4 is expressed on endothelial cells of the ceiling but not of the floor of the SCS. By scavenging CCR7 ligands, ACKR4 actively shapes chemokine gradients pointing from the SCS lumen toward the LN parenchyma that facilitate homing of cells into the TCZ.8

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Acknowledgements

This work was supported by Deutsche Forschungsgemeinschaft, (DFG, German Research Foundation) under Germany’s Excellence Strategy – EXC 2155 “RESIST” – Project ID 39087428, DFG grants SFB900-B1 and FOR2830-P006 to RF and Deutsche Akademische Austauschdienst grant GSSP2014-57034101-91557342 to GN

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  1. Institute of Immunology, Hannover Medical School, 30625, Hannover, Germany

    Ginka Nikolova, Siegfried Weiss, Berislav Bosnjak & Reinhold Förster

  2. Cluster of Excellence RESIST (EXC 2155), Hannover Medical School, 30625, Hannover, Germany

    Siegfried Weiss & Reinhold Förster

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  1. Ginka Nikolova
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Correspondence to Reinhold Förster.

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Nikolova, G., Weiss, S., Bosnjak, B. et al. Differential retention of lymph-borne CD8 memory T cell subsets in the subcapsular sinus of resting and inflamed lymph nodes. Cell Mol Immunol 18, 1317–1319 (2021). https://doi.org/10.1038/s41423-020-0451-6

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