The Second Touch Hypothesis: T Cell Activation, Homing and Polarization

Overview

Journal F1000Res

Specialties Biomedical Engineering
Science

Date 2015 Jan 15

PMID 25580220

Citations 38

Authors

Klaus Ley

Affiliations

Soon will be listed here.

Abstract

The second touch hypothesis states that T cell activation, proliferation, induction of homing receptors and polarization are distinguishable and, at least in part, sequential. The second touch hypothesis maintains that full T cell polarization requires T cell interaction with antigen-presenting cells (DCs, macrophages, B cells and certain activated stromal cells) in the non-lymphoid tissue where the antigen resides. Upon initial antigen encounter in peripheral lymph nodes (PLN), T cells become activated, proliferate and express homing receptors that enable them to recirculate to the (inflamed) tissue that contains the antigen. Differentiation into the T helper lineages Th1, Th2, Th17 and induced regulatory T cells (iTreg) requires additional antigen presentation by tissue macrophages and other antigen presenting cells (APCs) in the inflamed tissue. Here, I present a conceptual framework for the importance of peripheral (non-lymphoid) antigen presentation to antigen-experienced T cells.

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References

Germain R, Jenkins M . In vivo antigen presentation. Curr Opin Immunol. 2004; 16(1):120-5. DOI: 10.1016/j.coi.2003.11.001. View

Chistiakov D, Sobenin I, Orekhov A . Regulatory T cells in atherosclerosis and strategies to induce the endogenous atheroprotective immune response. Immunol Lett. 2013; 151(1-2):10-22. DOI: 10.1016/j.imlet.2013.01.014. View

Lucas M, Stuart L, Savill J, Lacy-Hulbert A . Apoptotic cells and innate immune stimuli combine to regulate macrophage cytokine secretion. J Immunol. 2003; 171(5):2610-5. DOI: 10.4049/jimmunol.171.5.2610. View

Croft M . The role of TNF superfamily members in T-cell function and diseases. Nat Rev Immunol. 2009; 9(4):271-85. PMC: 2737409. DOI: 10.1038/nri2526. View

Zhou L, Chong M, Littman D . Plasticity of CD4+ T cell lineage differentiation. Immunity. 2009; 30(5):646-55. DOI: 10.1016/j.immuni.2009.05.001. View

Wakim L, Waithman J, van Rooijen N, Heath W, Carbone F . Dendritic cell-induced memory T cell activation in nonlymphoid tissues. Science. 2008; 319(5860):198-202. DOI: 10.1126/science.1151869. View

Rodrigo Mora J, Bono M, Manjunath N, Weninger W, Cavanagh L, Rosemblatt M . Selective imprinting of gut-homing T cells by Peyer's patch dendritic cells. Nature. 2003; 424(6944):88-93. DOI: 10.1038/nature01726. View

Melton A, Bailey-Bucktrout S, Travis M, Fife B, Bluestone J, Sheppard D . Expression of αvβ8 integrin on dendritic cells regulates Th17 cell development and experimental autoimmune encephalomyelitis in mice. J Clin Invest. 2010; 120(12):4436-44. PMC: 2993595. DOI: 10.1172/JCI43786. View

Mempel T, Henrickson S, von Andrian U . T-cell priming by dendritic cells in lymph nodes occurs in three distinct phases. Nature. 2004; 427(6970):154-9. DOI: 10.1038/nature02238. View

10.

Geissmann F, Manz M, Jung S, Sieweke M, Merad M, Ley K . Development of monocytes, macrophages, and dendritic cells. Science. 2010; 327(5966):656-61. PMC: 2887389. DOI: 10.1126/science.1178331. View

11.

Oh S, Li M . TGF-β: guardian of T cell function. J Immunol. 2013; 191(8):3973-9. PMC: 3856438. DOI: 10.4049/jimmunol.1301843. View

12.

Gebhardt T, Whitney P, Zaid A, Mackay L, Brooks A, Heath W . Different patterns of peripheral migration by memory CD4+ and CD8+ T cells. Nature. 2011; 477(7363):216-9. DOI: 10.1038/nature10339. View

13.

Travis M, Reizis B, Melton A, Masteller E, Tang Q, Proctor J . Loss of integrin alpha(v)beta8 on dendritic cells causes autoimmunity and colitis in mice. Nature. 2007; 449(7160):361-5. PMC: 2670239. DOI: 10.1038/nature06110. View

14.

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

15.

Ley K, Kansas G . Selectins in T-cell recruitment to non-lymphoid tissues and sites of inflammation. Nat Rev Immunol. 2004; 4(5):325-35. DOI: 10.1038/nri1351. View

16.

Muller A, Filipe-Santos O, Eberl G, Aebischer T, Spath G, Bousso P . CD4+ T cells rely on a cytokine gradient to control intracellular pathogens beyond sites of antigen presentation. Immunity. 2012; 37(1):147-57. DOI: 10.1016/j.immuni.2012.05.015. View

17.

Vijayanand P, Seumois G, Simpson L, Abdul-Wajid S, Baumjohann D, Panduro M . Interleukin-4 production by follicular helper T cells requires the conserved Il4 enhancer hypersensitivity site V. Immunity. 2012; 36(2):175-87. PMC: 3288297. DOI: 10.1016/j.immuni.2011.12.014. View

18.

Croft M . Co-stimulatory members of the TNFR family: keys to effective T-cell immunity?. Nat Rev Immunol. 2003; 3(8):609-20. DOI: 10.1038/nri1148. View

19.

Shull M, Ormsby I, Kier A, Pawlowski S, Diebold R, Yin M . Targeted disruption of the mouse transforming growth factor-beta 1 gene results in multifocal inflammatory disease. Nature. 1992; 359(6397):693-9. PMC: 3889166. DOI: 10.1038/359693a0. View

20.

Lee K, Gudapati P, Dragovic S, Spencer C, Joyce S, Killeen N . Mammalian target of rapamycin protein complex 2 regulates differentiation of Th1 and Th2 cell subsets via distinct signaling pathways. Immunity. 2010; 32(6):743-53. PMC: 2911434. DOI: 10.1016/j.immuni.2010.06.002. View