Recirculating Memory T Cells Are a Unique Subset of CD4+ T Cells with a Distinct Phenotype and Migratory Pattern

Overview

Journal J Immunol

Specialty Allergy & Immunology

Date 2012 Dec 21

PMID 23255361

Citations 103

Authors

Shannon K Bromley

Sha Yan

Michio Tomura

Osami Kanagawa

Andrew D Luster

Affiliations

Soon will be listed here.

Abstract

Several populations of memory T cells have been described that differ in their migration and function. In this study, we have identified a unique subset of memory T cells, which we have named recirculating memory T cells (T(RCM)). By exposing Kaede transgenic mouse skin to violet light, we tracked the fate of cutaneous T cells. One population of memory CD4(+) T cells remained in the skin. A second population migrated from the skin into draining lymph nodes (LNs) in a CCR7-dependent manner. These migrating CD4(+) T cells expressed a novel cell surface phenotype (CCR7(int/+)CD62L(int)CD69(-)CD103(+/-) E-selectin ligands(+)) that is distinct from memory T cell subsets described to date. Unlike memory T cell subsets that remain resident within tissues long-term, or that migrate either exclusively between lymphoid tissues or into peripheral nonlymphoid sites, CD4(+) T(RCM) migrate from the skin into draining LNs. From the draining LNs, CD4(+) T(RCM) reenter into the circulation, distal LNs, and sites of non-specific cutaneous inflammation. In addition, CD4(+) T(RCM) upregulated CD40L and secreted IL-2 following polyclonal stimulation. Our results identify a novel subset of recirculating memory CD4(+) T cells equipped to deliver help to both distal lymphoid and cutaneous tissues.

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References

Gebhardt T, Wakim L, Eidsmo L, Reading P, Heath W, Carbone F . Memory T cells in nonlymphoid tissue that provide enhanced local immunity during infection with herpes simplex virus. Nat Immunol. 2009; 10(5):524-30. DOI: 10.1038/ni.1718. View

Forster R, Schubel A, Breitfeld D, Kremmer E, Renner-Muller I, Wolf E . CCR7 coordinates the primary immune response by establishing functional microenvironments in secondary lymphoid organs. Cell. 1999; 99(1):23-33. DOI: 10.1016/s0092-8674(00)80059-8. View

Pham T, Okada T, Matloubian M, Lo C, Cyster J . S1P1 receptor signaling overrides retention mediated by G alpha i-coupled receptors to promote T cell egress. Immunity. 2008; 28(1):122-33. PMC: 2691390. DOI: 10.1016/j.immuni.2007.11.017. View

Bromley S, Thomas S, Luster A . Chemokine receptor CCR7 guides T cell exit from peripheral tissues and entry into afferent lymphatics. Nat Immunol. 2005; 6(9):895-901. DOI: 10.1038/ni1240. View

Shiow L, Rosen D, Brdickova N, Xu Y, An J, Lanier L . CD69 acts downstream of interferon-alpha/beta to inhibit S1P1 and lymphocyte egress from lymphoid organs. Nature. 2006; 440(7083):540-4. DOI: 10.1038/nature04606. View

Tomura M, Itoh K, Kanagawa O . Naive CD4+ T lymphocytes circulate through lymphoid organs to interact with endogenous antigens and upregulate their function. J Immunol. 2010; 184(9):4646-53. DOI: 10.4049/jimmunol.0903946. View

Zhou B, Comeau M, De Smedt T, Liggitt H, Dahl M, Lewis D . Thymic stromal lymphopoietin as a key initiator of allergic airway inflammation in mice. Nat Immunol. 2005; 6(10):1047-53. DOI: 10.1038/ni1247. View

Tomura M, Honda T, Tanizaki H, Otsuka A, Egawa G, Tokura Y . Activated regulatory T cells are the major T cell type emigrating from the skin during a cutaneous immune response in mice. J Clin Invest. 2010; 120(3):883-93. PMC: 2827959. DOI: 10.1172/JCI40926. View

Brown M, Fintushel S, Lee M, Jennrich S, Geherin S, Hay J . Chemoattractant receptors and lymphocyte egress from extralymphoid tissue: changing requirements during the course of inflammation. J Immunol. 2010; 185(8):4873-82. PMC: 3327166. DOI: 10.4049/jimmunol.1000676. View

10.

Allende M, Dreier J, Mandala S, Proia R . Expression of the sphingosine 1-phosphate receptor, S1P1, on T-cells controls thymic emigration. J Biol Chem. 2004; 279(15):15396-401. DOI: 10.1074/jbc.M314291200. View

11.

Debes G, Arnold C, Young A, Krautwald S, Lipp M, Hay J . Chemokine receptor CCR7 required for T lymphocyte exit from peripheral tissues. Nat Immunol. 2005; 6(9):889-94. PMC: 2144916. DOI: 10.1038/ni1238. View

12.

Sallusto F, Lenig D, Forster R, Lipp M, Lanzavecchia A . Two subsets of memory T lymphocytes with distinct homing potentials and effector functions. Nature. 1999; 401(6754):708-12. DOI: 10.1038/44385. View

13.

Schon M, Arya A, Murphy E, Adams C, Strauch U, Agace W . Mucosal T lymphocyte numbers are selectively reduced in integrin alpha E (CD103)-deficient mice. J Immunol. 1999; 162(11):6641-9. View

14.

Cepek K, Shaw S, Parker C, Russell G, Morrow J, Rimm D . Adhesion between epithelial cells and T lymphocytes mediated by E-cadherin and the alpha E beta 7 integrin. Nature. 1994; 372(6502):190-3. DOI: 10.1038/372190a0. View

15.

Issekutz T, Chin W, Hay J . The characterization of lymphocytes migrating through chronically inflamed tissues. Immunology. 1982; 46(1):59-66. PMC: 1555346. View

16.

Cahill R, Poskitt D, Frost D, TRNKA Z . Two distinct pools of recirculating T lymphocytes: migratory characteristics of nodal and intestinal T lymphocytes. J Exp Med. 1977; 145(2):420-8. PMC: 2180614. DOI: 10.1084/jem.145.2.420. View

17.

Pauls K, Schon M, Kubitza R, Homey B, Wiesenborn A, Lehmann P . Role of integrin alphaE(CD103)beta7 for tissue-specific epidermal localization of CD8+ T lymphocytes. J Invest Dermatol. 2001; 117(3):569-75. DOI: 10.1046/j.0022-202x.2001.01481.x. View

18.

Clark R, Chong B, Mirchandani N, Brinster N, Yamanaka K, Dowgiert R . The vast majority of CLA+ T cells are resident in normal skin. J Immunol. 2006; 176(7):4431-9. DOI: 10.4049/jimmunol.176.7.4431. View

19.

Clark R, Watanabe R, Teague J, Schlapbach C, Tawa M, Adams N . Skin effector memory T cells do not recirculate and provide immune protection in alemtuzumab-treated CTCL patients. Sci Transl Med. 2012; 4(117):117ra7. PMC: 3373186. DOI: 10.1126/scitranslmed.3003008. View

20.

Suffia I, Reckling S, Salay G, Belkaid Y . A role for CD103 in the retention of CD4+CD25+ Treg and control of Leishmania major infection. J Immunol. 2005; 174(9):5444-55. DOI: 10.4049/jimmunol.174.9.5444. View