Migratory and Lymphoid-resident Dendritic Cells Cooperate to Efficiently Prime Naive CD4 T Cells

Overview

Journal Immunity

Publisher Cell Press

Specialty Allergy & Immunology

Date 2008 Oct 28

PMID 18951047

Citations 98

Authors

Eric J Allenspach

Maria P Lemos

Paige M Porrett

Laurence A Turka

Terri M Laufer

Affiliations

Soon will be listed here.

Abstract

To initiate an adaptive immune response, rare antigen-specific naive CD4(+) T cells must interact with equally rare dendritic cells (DCs) bearing cognate peptide-major histocompatibility complex (MHC) complexes. Lymph nodes (LNs) draining the site of antigen entry are populated by lymphoid-resident DCs as well as DCs that have immigrated from tissues, although the requirement for each population in initiating the T cell response remains unclear. Here, we show that antigen processing and presentation by both lymphoid-resident and migratory DCs was required for clonal selection and expansion of CD4(+) T cells after subcutaneous immunization. Early antigen presentation by lymphoid-resident DCs initiated activation and trapping of antigen-specific T cells in the draining LN, without sufficing for clonal expansion. Migratory DCs, however, interacted with the CD4(+) T cells retained in the LN to induce proliferation. Therefore, distinct DC subsets cooperate to alert and trap the appropriate cell and then license its expansion and differentiation.

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References

Vremec D, Shortman K . Dendritic cell subtypes in mouse lymphoid organs: cross-correlation of surface markers, changes with incubation, and differences among thymus, spleen, and lymph nodes. J Immunol. 1997; 159(2):565-73. View

McGill J, van Rooijen N, Legge K . Protective influenza-specific CD8 T cell responses require interactions with dendritic cells in the lungs. J Exp Med. 2008; 205(7):1635-46. PMC: 2442641. DOI: 10.1084/jem.20080314. 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

Sixt M, Kanazawa N, Selg M, Samson T, Roos G, Reinhardt D . The conduit system transports soluble antigens from the afferent lymph to resident dendritic cells in the T cell area of the lymph node. Immunity. 2005; 22(1):19-29. DOI: 10.1016/j.immuni.2004.11.013. View

Kissenpfennig A, Henri S, Dubois B, Laplace-Builhe C, Perrin P, Romani N . Dynamics and function of Langerhans cells in vivo: dermal dendritic cells colonize lymph node areas distinct from slower migrating Langerhans cells. Immunity. 2005; 22(5):643-54. DOI: 10.1016/j.immuni.2005.04.004. View

Sakoda Y, Hashimoto D, Asakura S, Takeuchi K, Harada M, Tanimoto M . Donor-derived thymic-dependent T cells cause chronic graft-versus-host disease. Blood. 2006; 109(4):1756-64. DOI: 10.1182/blood-2006-08-042853. View

Ravindran R, Rusch L, Itano A, Jenkins M, McSorley S . CCR6-dependent recruitment of blood phagocytes is necessary for rapid CD4 T cell responses to local bacterial infection. Proc Natl Acad Sci U S A. 2007; 104(29):12075-80. PMC: 1907313. DOI: 10.1073/pnas.0701363104. View

Moon J, Chu H, Pepper M, McSorley S, Jameson S, Kedl R . Naive CD4(+) T cell frequency varies for different epitopes and predicts repertoire diversity and response magnitude. Immunity. 2007; 27(2):203-13. PMC: 2200089. DOI: 10.1016/j.immuni.2007.07.007. View

Tacken P, de Vries I, Torensma R, Figdor C . Dendritic-cell immunotherapy: from ex vivo loading to in vivo targeting. Nat Rev Immunol. 2007; 7(10):790-802. DOI: 10.1038/nri2173. View

10.

Villadangos J, Heath W . Life cycle, migration and antigen presenting functions of spleen and lymph node dendritic cells: limitations of the Langerhans cells paradigm. Semin Immunol. 2005; 17(4):262-72. DOI: 10.1016/j.smim.2005.05.015. View

11.

Soderberg K, Payne G, Sato A, Medzhitov R, Segal S, Iwasaki A . Innate control of adaptive immunity via remodeling of lymph node feed arteriole. Proc Natl Acad Sci U S A. 2005; 102(45):16315-20. PMC: 1283434. DOI: 10.1073/pnas.0506190102. View

12.

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

13.

Catron D, Rusch L, Hataye J, Itano A, Jenkins M . CD4+ T cells that enter the draining lymph nodes after antigen injection participate in the primary response and become central-memory cells. J Exp Med. 2006; 203(4):1045-54. PMC: 2118291. DOI: 10.1084/jem.20051954. View

14.

Allan R, Waithman J, Bedoui S, Jones C, Villadangos J, Zhan Y . Migratory dendritic cells transfer antigen to a lymph node-resident dendritic cell population for efficient CTL priming. Immunity. 2006; 25(1):153-62. DOI: 10.1016/j.immuni.2006.04.017. View

15.

Bogunovic M, Ginhoux F, Wagers A, Loubeau M, Isola L, Lubrano L . Identification of a radio-resistant and cycling dermal dendritic cell population in mice and men. J Exp Med. 2006; 203(12):2627-38. PMC: 2118165. DOI: 10.1084/jem.20060667. View

16.

Quang Van V, Lesage S, Bouguermouh S, Gautier P, Rubio M, Levesque M . Expression of the self-marker CD47 on dendritic cells governs their trafficking to secondary lymphoid organs. EMBO J. 2006; 25(23):5560-8. PMC: 1679770. DOI: 10.1038/sj.emboj.7601415. View

17.

Bajenoff M, Egen J, Koo L, Laugier J, Brau F, Glaichenhaus N . Stromal cell networks regulate lymphocyte entry, migration, and territoriality in lymph nodes. Immunity. 2006; 25(6):989-1001. PMC: 2692293. DOI: 10.1016/j.immuni.2006.10.011. View

18.

Vremec D, Pooley J, HOCHREIN H, Wu L, Shortman K . CD4 and CD8 expression by dendritic cell subtypes in mouse thymus and spleen. J Immunol. 2000; 164(6):2978-86. DOI: 10.4049/jimmunol.164.6.2978. View

19.

Mach N, Gillessen S, Wilson S, Sheehan C, Mihm M, Dranoff G . Differences in dendritic cells stimulated in vivo by tumors engineered to secrete granulocyte-macrophage colony-stimulating factor or Flt3-ligand. Cancer Res. 2000; 60(12):3239-46. View

20.

Smith A, Wikstrom M, Fazekas de St Groth B . Visualizing T cell competition for peptide/MHC complexes: a specific mechanism to minimize the effect of precursor frequency. Immunity. 2001; 13(6):783-94. DOI: 10.1016/s1074-7613(00)00076-5. View