T Cells in Nonlymphoid Tissues Give Rise to Lymph-Node-Resident Memory T Cells

Overview

Journal Immunity

Publisher Cell Press

Specialty Allergy & Immunology

Date 2018 Feb 22

PMID 29466758

Citations 135

Authors

Lalit K Beura

Sathi Wijeyesinghe

Emily A Thompson

Marissa G Macchietto

Pamela C Rosato

Mark J Pierson

Jason M Schenkel

Jason S Mitchell

Vaiva Vezys

Brian T Fife

Steven Shen

David Masopust

Affiliations

Soon will be listed here.

Abstract

Immunosurveillance of secondary lymphoid organs (SLO) is performed by central memory T cells that recirculate through blood. Resident memory T (Trm) cells remain parked in nonlymphoid tissues and often stably express CD69. We recently identified Trm cells within SLO, but the origin and phenotype of these cells remains unclear. Using parabiosis of "dirty" mice, we found that CD69 expression is insufficient to infer stable residence of SLO Trm cells. Restimulation of nonlymphoid memory CD8 T cells within the skin or mucosa resulted in a substantial increase in bona fide Trm cells specifically within draining lymph nodes. SLO Trm cells derived from emigrants from nonlymphoid tissues and shared some transcriptional and phenotypic signatures associated with nonlymphoid Trm cells. These data indicate that nonlymphoid cells can give rise to SLO Trm cells and suggest vaccination strategies by which memory CD8 T cell immunosurveillance can be regionalized to specific lymph nodes.

Citing Articles

Tissue-Resident Memory CD8+ T Cells: Differentiation, Phenotypic Heterogeneity, Biological Function, Disease, and Therapy.

Xu L, Ye L, Huang Q MedComm (2020). 2025; 6(3):e70132.

PMID: 40066223 PMC: 11892159. DOI: 10.1002/mco2.70132.

Temporal profiling of human lymphoid tissues reveals coordinated defense against viral challenge.

Coates M, Richoz N, Tuong Z, Bowyer G, Lee C, Ferdinand J Nat Immunol. 2025; 26(2):215-229.

PMID: 39890933 PMC: 11785532. DOI: 10.1038/s41590-024-02064-9.

Targeting intracellular proteins with cell type-specific functions for cancer immunotherapy.

Carelock M, Master R, Kim M, Jin Z, Wang L, Maharjan C Life Med. 2025; 2(3):lnad019.

PMID: 39872303 PMC: 11749652. DOI: 10.1093/lifemedi/lnad019.

Deep profiling deconstructs features associated with memory CD8 T cell tissue residence.

Scott M, Steier Z, Pierson M, Stolley J, OFlanagan S, Soerens A Immunity. 2024; 58(1):162-181.e10.

PMID: 39708817 PMC: 11852946. DOI: 10.1016/j.immuni.2024.11.007.

Ex vivo expansion and hydrogel-mediated in vivo delivery of tissue-resident memory T cells for immunotherapy.

Li S, Yao Z, Wang H, Ecker J, Omotoso M, Lee J Sci Adv. 2024; 10(50):eadm7928.

PMID: 39671478 PMC: 11641059. DOI: 10.1126/sciadv.adm7928.

References

Pan Y, Tian T, Park C, Lofftus S, Mei S, Liu X . Survival of tissue-resident memory T cells requires exogenous lipid uptake and metabolism. Nature. 2017; 543(7644):252-256. PMC: 5509051. DOI: 10.1038/nature21379. View

Junt T, Moseman E, Iannacone M, Massberg S, Lang P, Boes M . Subcapsular sinus macrophages in lymph nodes clear lymph-borne viruses and present them to antiviral B cells. Nature. 2007; 450(7166):110-4. DOI: 10.1038/nature06287. View

Li S, Folkvord J, Rakasz E, Abdelaal H, Wagstaff R, Kovacs K . Simian Immunodeficiency Virus-Producing Cells in Follicles Are Partially Suppressed by CD8+ Cells In Vivo. J Virol. 2016; 90(24):11168-11180. PMC: 5126374. DOI: 10.1128/JVI.01332-16. View

Schenkel J, Fraser K, Masopust D . Cutting edge: resident memory CD8 T cells occupy frontline niches in secondary lymphoid organs. J Immunol. 2014; 192(7):2961-4. PMC: 3965619. DOI: 10.4049/jimmunol.1400003. View

Wakim L, Woodward-Davis A, Liu R, Hu Y, Villadangos J, Smyth G . The molecular signature of tissue resident memory CD8 T cells isolated from the brain. J Immunol. 2012; 189(7):3462-71. PMC: 3884813. DOI: 10.4049/jimmunol.1201305. View

Hickman H, Li L, Reynoso G, Rubin E, Skon C, Mays J . Chemokines control naive CD8+ T cell selection of optimal lymph node antigen presenting cells. J Exp Med. 2011; 208(12):2511-24. PMC: 3256957. DOI: 10.1084/jem.20102545. View

Mueller S, Gebhardt T, Carbone F, Heath W . Memory T cell subsets, migration patterns, and tissue residence. Annu Rev Immunol. 2012; 31:137-61. DOI: 10.1146/annurev-immunol-032712-095954. View

Petrovas C, Ferrando-Martinez S, Gerner M, Casazza J, Pegu A, Deleage C . Follicular CD8 T cells accumulate in HIV infection and can kill infected cells in vitro via bispecific antibodies. Sci Transl Med. 2017; 9(373). PMC: 5497679. DOI: 10.1126/scitranslmed.aag2285. View

Thompson E, Beura L, Nelson C, Anderson K, Vezys V . Shortened Intervals during Heterologous Boosting Preserve Memory CD8 T Cell Function but Compromise Longevity. J Immunol. 2016; 196(7):3054-63. PMC: 4799748. DOI: 10.4049/jimmunol.1501797. View

10.

Woon H, Braun A, Li J, Smith C, Edwards J, Sierro F . Compartmentalization of Total and Virus-Specific Tissue-Resident Memory CD8+ T Cells in Human Lymphoid Organs. PLoS Pathog. 2016; 12(8):e1005799. PMC: 4991796. DOI: 10.1371/journal.ppat.1005799. View

11.

Silva K, Sundberg J . Surgical methods for full-thickness skin grafts to induce alopecia areata in C3H/HeJ mice. Comp Med. 2013; 63(5):392-7. PMC: 3796749. View

12.

von Andrian U, Mackay C . T-cell function and migration. Two sides of the same coin. N Engl J Med. 2000; 343(14):1020-34. DOI: 10.1056/NEJM200010053431407. View

13.

Kastenmuller W, Brandes M, Wang Z, Herz J, Egen J, Germain R . Peripheral prepositioning and local CXCL9 chemokine-mediated guidance orchestrate rapid memory CD8+ T cell responses in the lymph node. Immunity. 2013; 38(3):502-13. PMC: 3793246. DOI: 10.1016/j.immuni.2012.11.012. View

14.

Sung J, Zhang H, Moseman E, Alvarez D, Iannacone M, Henrickson S . Chemokine guidance of central memory T cells is critical for antiviral recall responses in lymph nodes. Cell. 2012; 150(6):1249-63. PMC: 3445043. DOI: 10.1016/j.cell.2012.08.015. View

15.

Beura L, Anderson K, Schenkel J, Locquiao J, Fraser K, Vezys V . Lymphocytic choriomeningitis virus persistence promotes effector-like memory differentiation and enhances mucosal T cell distribution. J Leukoc Biol. 2014; 97(2):217-25. PMC: 4304422. DOI: 10.1189/jlb.1HI0314-154R. View

16.

Takamura S, Yagi H, Hakata Y, Motozono C, McMaster S, Masumoto T . Specific niches for lung-resident memory CD8+ T cells at the site of tissue regeneration enable CD69-independent maintenance. J Exp Med. 2016; 213(13):3057-3073. PMC: 5154946. DOI: 10.1084/jem.20160938. View

17.

Gautier L, Cope L, Bolstad B, Irizarry R . affy--analysis of Affymetrix GeneChip data at the probe level. Bioinformatics. 2004; 20(3):307-15. DOI: 10.1093/bioinformatics/btg405. View

18.

Freeman B, Hammarlund E, Raue H, Slifka M . Regulation of innate CD8+ T-cell activation mediated by cytokines. Proc Natl Acad Sci U S A. 2012; 109(25):9971-6. PMC: 3382521. DOI: 10.1073/pnas.1203543109. View

19.

Thome J, Grinshpun B, Kumar B, Kubota M, Ohmura Y, Lerner H . Longterm maintenance of human naive T cells through homeostasis in lymphoid tissue sites. Sci Immunol. 2017; 1(6). PMC: 5367636. DOI: 10.1126/sciimmunol.aah6506. View

20.

Skon C, Lee J, Anderson K, Masopust D, Hogquist K, Jameson S . Transcriptional downregulation of S1pr1 is required for the establishment of resident memory CD8+ T cells. Nat Immunol. 2013; 14(12):1285-93. PMC: 3844557. DOI: 10.1038/ni.2745. View