Access through your institution Buy or subscribe 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

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 This is a preview of subscription content, access via your institution ACCESS OPTIONS Access through your institution Subscribe to this journal Receive 12 digital issues and online

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taxes which are calculated during checkout ADDITIONAL ACCESS OPTIONS: * Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support REFERENCES * Jameson, S.

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node. _eLife_ 5, e18156 https://doi.org/10.7554/eLife.18156 (2016). Article  CAS  PubMed  PubMed Central  Google Scholar  Download references 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 AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Institute of Immunology, Hannover Medical School, 30625,

Hannover, Germany Ginka Nikolova, Siegfried Weiss, Berislav Bosnjak & Reinhold Förster * Cluster of Excellence RESIST (EXC 2155), Hannover Medical School, 30625, Hannover, Germany

Siegfried Weiss & Reinhold Förster Authors * Ginka Nikolova View author publications You can also search for this author inPubMed Google Scholar * Siegfried Weiss View author

publications You can also search for this author inPubMed Google Scholar * Berislav Bosnjak View author publications You can also search for this author inPubMed Google Scholar * Reinhold

Förster View author publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to Reinhold Förster. ETHICS DECLARATIONS COMPETING INTERESTS

The authors declare no competing interests. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE 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 Download citation * Received: 31 March 2020 * Accepted: 03 April 2020 * Published: 12 May 2020 * Issue Date: May 2021 * DOI:

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