Induction of appropriate Th-cell phenotypes: Cellular decision-making in heterogeneous environments

Parasite Immunology

Volumn 35, Issue 11, 2013, Pages 318-330

  Van den Ham, H J ^a   Andeweg, A C ^a   de Boer, R J ^b  

^a ERASMUS MEDICAL CENTER   (Netherlands)

^b UTRECHT UNIVERSITY   (Netherlands)

Author keywords

Modelling; Stochasticity; T helper cells; Th cell phenotypes

Indexed keywords

AUTOCRINE EFFECT; CYTOKINE PRODUCTION; HELPER CELL; HUMAN; INNATE IMMUNITY; LYMPHOCYTE DIFFERENTIATION; MATHEMATICAL MODEL; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL; REGULATORY MECHANISM; REVIEW; TH1 CELL; TH2 CELL; ADAPTIVE IMMUNITY; ANIMAL; CYTOLOGY; FEEDBACK SYSTEM; IMMUNOLOGY; LYMPHOCYTE ACTIVATION; REGULATORY T LYMPHOCYTE;

CYTOKINE; EPITOPE; PATHOGEN ASSOCIATED MOLECULAR PATTERN; TRANSCRIPTOME;

ADAPTIVE IMMUNITY; ANIMALS; CYTOKINES; EPITOPES; FEEDBACK; HUMANS; IMMUNITY, INNATE; LYMPHOCYTE ACTIVATION; PATHOGEN-ASSOCIATED MOLECULAR PATTERN MOLECULES; T-LYMPHOCYTES, HELPER-INDUCER; T-LYMPHOCYTES, REGULATORY; TRANSCRIPTOME;

EID: 84885400140     PISSN: 01419838     EISSN: 13653024     Source Type: Journal    
DOI: 10.1111/pim.12053     Document Type: Review

References (131)

1. Paul WE. Fundamental Immunology. Lippincott Williams and Wilkins, Philadelphia, 2012: 1-1312.
2. Calis JJA, De Boer RJ & Kesmir C. Degenerate T-cell recognition of peptides on MHC molecules creates large holes in the T-cell repertoire. PLoS Comput Biol 2012; 8: e1002412.
3. Mosmann TR, Cherwinski H, Bond MW, et al. Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J Immunol 1986; 136: 2348-2357.
4. Bacellar O, Brodskyn C, Guerreiro J, et al. Interleukin-12 restores interferon production and cytotoxic responses in visceral leishmaniasis. J Infect Dis 1996; 173: 1515-1518.
5. Carvalho EM, Badaró R, Reed SG, et al. Absence of gamma interferon and interleukin 2 production during active visceral leishmaniasis. J Clin Invest 1985; 76: 2066-2069.
6. Ouyang W, Löhning M, Gao Z, et al. Stat6-independent GATA-3 autoactivation directs IL-4-independent Th2 development and commitment. Immunity 2000; 12: 27-37.
7. Szabo SJ, Kim ST, Costa GL, et al. A novel transcription factor, T-bet, directs Th1 lineage commitment. Cell 2000; 100: 655-669.
8. Jenner RG, Townsend MJ, Jackson I, et al. The transcription factors T-bet and GATA-3 control alternative pathways of T-cell differentiation through a shared set of target genes. Proc Natl Acad Sci U S A 2009; 106: 17876-17881.
9. Wei G, Abraham BJ, Yagi R, et al. Genome-wide analyses of transcription factor GATA3-mediated gene regulation in distinct T cell types. Immunity 2011; 35: 299-311.
10. Sakaguchi S, Miyara M, Costantino CM, et al. FOXP3+ regulatory T cells in the human immune system. Nat Rev Immunol 2010; 10: 490-500.
11. Sakaguchi S, Sakaguchi N, Asano M, et al. Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases. J Immunol 1995; 155: 1151-1164.
12. Hori S, Nomura T & Sakaguchi S. Control of regulatory T cell development by the transcription factor Foxp3. Science 2003; 299: 1057-1061.
13. Zheng Y, Josefowicz SZ, Kas A, et al. Genome-wide analysis of Foxp3 target genes in developing and mature regulatory T cells. Nature 2007; 445: 936-940.
14. Gavin MA, Rasmussen JP, Fontenot JD, et al. Foxp3-dependent programme of regulatory T-cell differentiation. Nature 2007; 445: 771-775.
15. -Brunkow ME, Jeffery EW, Hjerrild KA, et al. Disruption of a new forkhead/winged-helix protein, scurfin, results in the fatal lymphoproliferative disorder of the scurfy mouse. Nat Genet 2001; 27: 68-73.
16. Bennett CL, Christie J, Ramsdell F, et al. The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of FOXP3. Nat Genet 2001; 27: 20-21.
17. Dong C. Diversification of T-helper-cell lineages: finding the family root of IL-17-producing cells. Nat Rev Immunol 2006; 6: 329-333.
18. Veldhoen M, Hocking RJ, Atkins CJ, et al. TGFbeta in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-producing T cells. Immunity 2006; 24: 179-189.
19. Ivanov II, McKenzie BS, Zhou L, et al. The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17+ T helper cells. Cell 2006; 126: 1121-1133.
20. Schraml BU, Hildner K, Ise W, et al. The AP-1 transcription factor Batf controls T(H)17 differentiation. Nature 2009; 460: 405-409.
21. Solt LA, Kumar N, Nuhant P, et al. Suppression of TH17 differentiation and autoimmunity by a synthetic ROR ligand. Nature 2011; 472: 491-494.
22. Veldhoen M, Hirota K, Westendorf AM, et al. The aryl hydrocarbon receptor links TH17-cell-mediated autoimmunity to environmental toxins. Nature 2008; 453: 106-109.
23. Eyerich S, Eyerich K, Pennino D, et al. Th22 cells represent a distinct human T cell subset involved in epidermal immunity and remodeling. J Clin Invest 2009; 119: 3573-3585.
24. Basu R, O'Quinn DB, Silberger DJ, et al. Th22 cells are an important source of IL-22 for host protection against enteropathogenic bacteria. Immunity 2012; 37: 1061-1075.
25. Larsen M, Arnaud L, Hié M, et al. Multiparameter grouping delineates heterogeneous populations of human IL-17 and/or IL-22 T-cell producers that share antigen specificities with other T-cell subsets. Eur J Immunol 2011; 41: 2596-2605.
26. Shaw MH, Kamada N, Kim Y, et al. Microbiota-induced IL-1β, but not IL-6, is critical for the development of steady-state TH17 cells in the intestine. J Exp Med 2012; 209: 251-258.
27. Veldhoen M, Uyttenhove C, Van Snick J, et al. Transforming growth factor-beta "reprograms" the differentiation of T helper 2 cells and promotes an interleukin 9-producing subset. Nat Immunol 2008; 9: 1341-1346.
28. Soroosh P & Doherty TA. Th9 and allergic disease. Immunology 2009; 127: 450-458.
29. Chang H-C, Sehra S, Goswami R, et al. The transcription factor PU.1 is required for the development of IL-9-producing T cells and allergic inflammation. Nat Immunol 2010; 11: 527-534.
30. Yao W, Zhang Y, Jabeen R, et al. Interleukin-9 is required for allergic airway inflammation mediated by the cytokine TSLP. Immunity 2013; 32: 360-372.
31. Elyaman W, Bassil R, Bradshaw EM, et al. Notch receptors and Smad3 signaling cooperate in the induction of interleukin-9-producing T cells. Immunity 2012; 361: 623-634.
32. Van den Ham HJ, De Waal L, Andeweg AC, et al. Identification of helper T cell master regulator candidates using the polar score method. J Immunol Methods 2010; 361: 98-109.
33. Jäger A, Dardalhon V, Sobel RA, et al. Th1, Th17, and Th9 effector cells induce experimental autoimmune encephalomyelitis with different pathological phenotypes. J Immunol 2009; 183: 7169-7177.
34. Lotz MT & Peebles RS. Mechanisms of respiratory syncytial virus modulation of airway immune responses. Curr Allergy Asthma Rep 2012; 12: 380-387.
35. Milner JD, Brenchley JM, Laurence A, et al. Impaired T(H)17 cell differentiation in subjects with autosomal dominant hyper-IgE syndrome. Nature 2008; 452: 773-776.
36. Nurieva RI, Chung Y, Hwang D, et al. Generation of T follicular helper cells is mediated by interleukin-21 but independent of T helper 1, 2, or 17 cell lineages. Immunity 2008; 29: 138-149.
37. Ma CS, Deenick EK, Batten M, et al. The origins, function, and regulation of T follicular helper cells. J Exp Med 2012; 209: 1241-1253.
38. Zaretsky AG, Taylor JJ, King IL, et al. T follicular helper cells differentiate from Th2 cells in response to helminth antigens. J Exp Med 2009; 206: 991-999.
39. Lu KT, Kanno Y, Cannons JL, et al. Functional and epigenetic studies reveal multistep differentiation and plasticity of in vitro-generated and in vivo-derived follicular T helper cells. Immunity 2011; 35: 622-632.
40. Yu D, Rao S, Tsai LM, et al. The transcriptional repressor Bcl-6 directs T follicular helper cell lineage commitment. Immunity 2009; 31: 457-468.
41. Richter A, Löhning M & Radbruch A. Instruction for cytokine expression in T helper lymphocytes in relation to proliferation and cell cycle progression. J Exp Med 1999; 190: 1439-1450.
42. Gett AV & Hodgkin PD. Cell division regulates the T cell cytokine repertoire, revealing a mechanism underlying immune class regulation. Proc Natl Acad Sci U S A 1998; 95: 9488-9493.
43. Grogan JL, Mohrs M, Harmon B, et al. Early transcription and silencing of cytokine genes underlie polarization of T helper cell subsets. Immunity 2001; 14: 205-215.
44. Mariani L, Schulz EG, Lexberg MH, et al. Short-term memory in gene induction reveals the regulatory principle behind stochastic IL-4 expression. Mol Syst Biol 2010; 6: 359.
45. Paixão T, Carvalho TP, Calado DP, et al. Quantitative insights into stochastic monoallelic expression of cytokine genes. Immunol Cell Biol 2007; 85: 315-322.
46. Guo L, Hu-Li J & Paul WE. Probabilistic regulation of IL-4 production in Th2 cells: accessibility at the Il4 locus. Immunity 2004; 20: 193-203.
47. Han Q, Bagheri N, Bradshaw EM, et al. Polyfunctional responses by human T cells result from sequential release of cytokines. Proc Natl Acad Sci U S A 2012; 109: 1607-1612.
48. Shin H & Iwasaki A. A vaccine strategy that protects against genital herpes by establishing local memory T cells. Nature 2012; 491: 463-467.
49. Ariotti S, Beltman JB, Chodaczek G, et al. Tissue-resident memory CD8+ T cells continuously patrol skin epithelia to quickly recognize local antigen. Proc Natl Acad Sci U S A 2012; 109: 19739-19744.
50. Islam SA & Luster AD. T cell homing to epithelial barriers in allergic disease. Nat Med 2012; 18: 705-715.
51. Gebhardt T, Whitney PG, Zaid A, et al. Different patterns of peripheral migration by memory CD4+ and CD8+ T cells. Nature 2011; 477: 216-219.
52. Gebhardt T, Mueller SN, Heath WR, et al. Peripheral tissue surveillance and residency by memory T cells. Trends Immunol 2013; 34: 27-32.
53. Teijaro JR, Turner D, Pham Q, et al. Cutting edge: tissue-retentive lung memory CD4 T cells mediate optimal protection to respiratory virus infection. J Immunol 2011; 187: 5510-5514.
54. Mackay LK, Stock AT, Ma JZ, et al. Long-lived epithelial immunity by tissue-resident memory T (TRM) cells in the absence of persisting local antigen presentation. Proc Natl Acad Sci U S A 2012; 109: 7037-7042.
55. Schenkel JM, Fraser KA, Vezys V, et al. Sensing and alarm function of resident memory CD8(+) T cells. Nat Immunol 2013; 14: 509-513.
56. Schulz EG, Mariani L, Radbruch A, et al. Sequential polarization and imprinting of type 1 T helper lymphocytes by interferon-gamma and interleukin-12. Immunity 2009; 30: 673-683.
57. Rudra D, DeRoos P, Chaudhry A, et al. Transcription factor Foxp3 and its protein partners form a complex regulatory network. Nat Immunol 2012; 13: 1010-1019.
58. Hwang ES, Szabo SJ, Schwartzberg PL, et al. T helper cell fate specified by kinase-mediated interaction of T-bet with GATA-3. Science 2005; 307: 430-433.
59. Zhou L, Lopes JE, Chong MMW, et al. TGF-beta-induced Foxp3 inhibits T(H)17 cell differentiation by antagonizing RORgammat function. Nature 2008; 453: 236-240.
60. Lazarevic V, Chen X, Shim J-H, et al. T-bet represses T(H)17 differentiation by preventing Runx1-mediated activation of the gene encoding RORγt. Nat Immunol 2010; 12: 96-104.
61. Ansel KM, Djuretic I, Tanasa B, et al. Regulation of Th2 differentiation and Il4 locus accessibility. Annu Rev Immunol 2006; 24: 607-656.
62. Wei G, Wei L, Zhu J, et al. Global mapping of H3K4me3 and H3K27me3 reveals specificity and plasticity in lineage fate determination of differentiating CD4+ T cells. Immunity 2009; 30: 155-167.
63. Elo LL, Järvenpää H, Tuomela S, et al. Genome-wide profiling of interleukin-4 and STAT6 transcription factor regulation of human Th2 cell programming. Immunity 2010; 32: 852-862.
64. Tuomela S, Salo V, Tripathi SK, et al. Identification of early gene expression changes during human Th17 cell differentiation. Blood 2012; 119: e151-e160.
65. Van den Ham H-J, De Waal L, Zaaraoui-Boutahar F, et al. Early divergence of Th1 and Th2 transcriptomes involves a small core response and sets of transiently expressed genes. Eur J Immunol 2013; 43: 1074-1084.
66. Yates a, Bergmann C, Van Hemmen JL, et al. Cytokine-modulated regulation of helper T cell populations. J Theor Biol 2000; 206: 539-560.
67. Bergmann C, Van Hemmen JL & Segel LA. Th1 or Th2: how an appropriate T helper response can be made. Bull Math Biol 2001; 63: 405-430.
68. Höfer T, Nathansen H, Löhning M, et al. GATA-3 transcriptional imprinting in Th2 lymphocytes: a mathematical model. Proc Natl Acad Sci U S A 2002; 99: 9364-9368.
69. Naldi A, Carneiro J, Chaouiya C, et al. Diversity and plasticity of Th cell types predicted from regulatory network modelling. PLoS Comput Biol 2010; 6: e1000912.
70. Carneiro J, Leon K, Caramalho I, et al. When three is not a crowd: a Crossregulation model of the dynamics and repertoire selection of regulatory CD4+ T cells. Immunol Rev 2007; 216: 48-68.
71. Van den Ham H-J & De Boer RJ. From the two-dimensional Th1 and Th2 phenotypes to high-dimensional models for gene regulation. Int Immunol 2008; 20: 1269-1277.
72. Hong T, Xing J, Li L, et al. A simple theoretical framework for understanding heterogeneous differentiation of CD4+T cells. BMC Syst Biol 2012; 6: 66.
73. Van den Ham HJ & De Boer RJ. Cell division curtails helper phenotype plasticity and expedites helper T-cell differentiation. Immunol Cell Biol 2012; 90: 860-868.
74. Durant L, Watford WT, Ramos HL, et al. Diverse targets of the transcription factor STAT3 contribute to T cell pathogenicity and homeostasis. Immunity 2010; 32: 605-615.
75. Lund RJ, Löytömäki M, Naumanen T, et al. Genome-wide identification of novel genes involved in early Th1 and Th2 cell differentiation. J Immunol 2007; 178: 3648-3660.
76. Busse D, De la Rosa M, Hobiger K, et al. Competing feedback loops shape IL-2 signaling between helper and regulatory T lymphocytes in cellular microenvironments. Proc Natl Acad Sci U S A 2010; 107: 3058-3063.
77. Yates A, Callard R & Stark J. Combining cytokine signalling with T-bet and GATA-3 regulation in Th1 and Th2 differentiation: a model for cellular decision-making. J Theor Biol 2004; 231: 181-196.
78. Alon U. Network motifs: theory and experimental approaches. Nat Rev Genet 2007; 8: 450-461.
79. Oestreich KJ & Weinmann AS. Master regulators or lineage-specifying? Changing views on CD4(+) T cell transcription factors. Nat Rev Immunol 2012; 12: 799-804.
80. Coomes SM, Pelly VS & Wilson MS. Plasticity within the αβ+CD4+ T-cell lineage: when, how and what for? Open Biology 2013; 3: 120157.
81. Wang Y-H, Voo KS, Liu B, et al. A novel subset of CD4(+) T(H)2 memory/effector cells that produce inflammatory IL-17 cytokine and promote the exacerbation of chronic allergic asthma. J Exp Med 2010; 207: 2479-2491.
82. Darrah PA, Patel DT, De Luca PM, et al. Multifunctional TH1 cells define a correlate of vaccine-mediated protection against Leishmania major. Nat Med 2007; 13: 843-850.
83. Hegazy AN, Peine M, Helmstetter C, et al. Interferons direct Th2 cell reprogramming to generate a stable GATA-3(+)T-bet(+) cell subset with combined Th2 and Th1 cell functions. Immunity 2010; 32: 116-128.
84. O'Garra A, Gabryšová L & Spits H. Quantitative events determine the differentiation and function of helper T cells. Nat Immunol 2011; 12: 288-294.
85. Pesenacker AM, Bending D, Ursu S, et al. CD161 defines the subset of FoxP3+ T cells capable of producing proinflammatory cytokines. Blood 2013; 121: 2647-2658.
86. + regulatory T cell fate during inflammation in mice. J Clin Invest 2011; 121: 4503-4515.
87. Moreau HD, Lemaître F, Terriac E, et al. Dynamic in situ cytometry uncovers T cell receptor signaling during immunological synapses and kinapses in vivo. Immunity 2012; 37: 351-363.
88. Beltman JB, Marée AFM & De Boer RJ. Analysing immune cell migration. Nat Rev Immunol 2009; 9: 789-798.
89. Brennan MD, Cheong R & Levchenko A. Systems biology. How information theory handles cell signaling and uncertainty. Science 2012; 338: 334-335.
90. Hanna J, Saha K, Pando B, et al. Direct cell reprogramming is a stochastic process amenable to acceleration. Nature 2009; 462: 595-601.
91. Chang HH, Hemberg M, Barahona M, et al. Transcriptome-wide noise controls lineage choice in mammalian progenitor cells. Nature 2008; 453: 544-547.
92. Zand MS, Briggs BJ, Bose A, et al. Discrete event modeling of CD4+ memory T cell generation. J Immunol 2004; 173: 3763-3772.
93. Hawkins ED, Turner ML, Dowling MR, et al. A model of immune regulation as a consequence of randomized lymphocyte division and death times. Proc Natl Acad Sci U S A 2007; 104: 5032-5037.
94. Subramanian VG, Duffy KR, Turner ML, et al. Determining the expected variability of immune responses using the cyton model. J Math Biol 2008; 56: 861-892.
95. Duffy KR, Wellard CJ, Markham JF, et al. Activation-induced B cell fates are selected by intracellular stochastic competition. Science 2012; 335: 338-341.
96. Müller AJ, Filipe-Santos O, Eberl G, et al. CD4+ T cells rely on a cytokine gradient to control intracellular pathogens beyond sites of antigen presentation. Immunity 2012; 37: 147-157.
97. Burroughs NJ & Van der Merwe PA. Stochasticity and spatial heterogeneity in T-cell activation. Immunol Rev 2007; 216: 69-80.
98. Almeida ARM, Amado IF, Reynolds J, et al. Quorum-sensing in CD4(+) T cell homeostasis: a hypothesis and a model. Front Immunol 2012; 3: 125.
99. Borghans JAM & De Boer RJ. Memorizing innate instructions requires a sufficiently specific adaptive immune system. Int Immunol 2002; 14: 525-532.
100. Banchereau J, Pascual V & O'Garra A. From IL-2 to IL-37: the expanding spectrum of anti-inflammatory cytokines. Nat Immunol 2012; 13: 925-931.
101. Brooks DG, Walsh KB, Elsaesser H, et al. IL-10 directly suppresses CD4 but not CD8 T cell effector and memory responses following acute viral infection. Proc Natl Acad Sci U S A 2010; 107: 3018-3023.
102. Höfer T, Krichevsky O & Altan-Bonnet G. Competition for IL-2 between regulatory and effector T cells to chisel immune responses. Front Immunol 2012; 3: 1-9.
103. Bocharov G, Quiel J, Luzyanina T, et al. Feedback regulation of proliferation vs. differentiation rates explains the dependence of CD4 T-cell expansion on precursor number. Proc Natl Acad Sci U S A 2011; 108: 3318-3323.
104. Quiel J, Caucheteux S, Laurence A, et al. Antigen-stimulated CD4 T-cell expansion is inversely and log-linearly related to precursor number. Proc Natl Acad Sci U S A 2011; 108: 3312-3317.
105. De Boer RJ & Perelson AS. Antigen-stimulated CD4 T cell expansion can be limited by their grazing of peptide-MHC complexes. J Immunol 2013; 190: 5454-5458.
106. Farrar JD, Ouyang W, Löhning M, et al. An instructive component in T helper cell type 2 (Th2) development mediated by GATA-3. J Exp Med 2001; 193: 643-650.
107. Akira S, Uematsu S & Takeuchi O. Pathogen recognition and innate immunity. Cell 2006; 124: 783-801.
108. Brightbill HD, Libraty DH, Krutzik SR, et al. Host defense mechanisms triggered by microbial lipoproteins through toll-like receptors. Science 1999; 285: 732-736.
109. Kim HW, Canchola JG, Brandt CD, et al. Respiratory syncytial virus disease in infants despite prior administration of antigenic inactivated vaccine. Am J Epidem 1969; 89: 422-434.
110. Openshaw PJ, Clarke SL & Record FM. Pulmonary eosinophilic response to respiratory syncytial virus infection in mice sensitized to the major surface glycoprotein G. Int Immunol 1992; 4: 493-500.
111. Srikiatkhachorn A & Braciale TJ. Virus-specific CD8+ T lymphocytes downregulate T helper cell type 2 cytokine secretion and pulmonary eosinophilia during experimental murine respiratory syncytial virus infection. J Exp Med 1997; 186: 421-432.
112. Loebbermann J, Durant L, Thornton H, et al. Defective immunoregulation in RSV vaccine-augmented viral lung disease restored by selective chemoattraction of regulatory T cells. Proc Natl Acad Sci U S A 2013; 110: 2987-2992.
113. Oshansky CM, Barber JP, Crabtree J, et al. Respiratory syncytial virus F and G proteins induce interleukin 1alpha, CC, and CXC chemokine responses by normal human bronchoepithelial cells. J Infect Dis 2010; 201: 1201-1207.
114. Tripp RA, Jones LP, Haynes LM, et al. CX3C chemokine mimicry by respiratory syncytial virus G glycoprotein. Nat Immunol 2001; 2: 732-738.
115. Teijaro JR, Ng C, Lee AM, et al. Persistent LCMV infection is controlled by blockade of Type I interferon signaling. Science 2013; 340: 207-211.
116. Jackson RJ, Ramsay AJ, Christensen CD, et al. Expression of mouse interleukin-4 by a recombinant ectromelia virus suppresses cytolytic lymphocyte responses and overcomes genetic resistance to mousepox. J Virol 2001; 75: 1205-1210.
117. Chen N, Bellone CJ, Schriewer J, et al. Poxvirus interleukin-4 expression overcomes inherent resistance and vaccine-induced immunity: pathogenesis, prophylaxis, and antiviral therapy. Virology 2011; 409: 328-337.
118. Sedý JR, Spear PG & Ware CF. Cross-regulation between herpesviruses and the TNF superfamily members. Nat Rev Immunol 2008; 8: 861-873.
119. Baxt LA, Garza-Mayers AC & Goldberg MB. Bacterial subversion of host innate immune pathways. Science 2013; 340: 697-701.
120. Segel LA & Bar-Or RL. On the role of feedback in promoting conflicting goals of the adaptive immune system. J Immunol 1999; 163: 1342-1349.
121. Matzinger P & Kamala T. Tissue-based class control: the other side of tolerance. Nat Rev Immunol 2011; 11: 221-230.
122. Buckley CD, Gilroy DW, Serhan CN, et al. The resolution of inflammation. Nat Rev Immunol 2012; 13: 59-66.
123. Han S, Asoyan A, Rabenstein H, et al. Role of antigen persistence and dose for CD4+ T-cell exhaustion and recovery. Proc Natl Acad Sci U S A 2010; 107: 20453-20458.
124. Cope A, Le Friec G, Cardone J, et al. The Th1 life cycle: molecular control of IFN-γ to IL-10 switching. Trends Immunol 2011; 32: 278-286.
125. Bluestone JA, Mackay CR, O'Shea JJ, et al. The functional plasticity of T cell subsets. Nat Rev Immunol 2009; 9: 811-816.
126. Bennett CL & Chakraverty R. Dendritic cells in tissues: in situ stimulation of immunity and immunopathology. Trends Immunol 2012; 33: 8-13.
127. Engel DR, Koscielny A, Wehner S, et al. T helper type 1 memory cells disseminate postoperative ileus over the entire intestinal tract. Nat Med 2010; 16: 1407-1413.
128. Inman CF, Singha S, Lewis M, et al. Dendritic cells interact with CD4 T cells in intestinal mucosa. J Leuk Biol 2010; 88: 571-578.
129. Koltsova EK, Garcia Z, Chodaczek G, et al. Dynamic T cell-APC interactions sustain chronic inflammation in atherosclerosis. J Clin Invest 2012; 122: 3114-3126.
130. Goding SR, Wilson KA, Xie Y, et al. Restoring immune function of tumor-specific CD4+ T cells during recurrence of melanoma. J Immunol 2013; 190: 4899-4909.
131. Wang C, Sanders CM, Yang Q, et al. High throughput sequencing reveals a complex pattern of dynamic interrelationships among human T cell subsets. Proc Natl Acad Sci U S A 2010; 107: 1518-1523.