Regulation of Th1/Th2 cells in asthma development: A mathematical model

Mathematical Biosciences and Engineering

Volumn 10, Issue 4, 2013, Pages 1095-1133

  Kim, Yangjin ^a   Lee, Seongwon ^b   Kim, You Sun ^b   Lawler, Sean ^c   Gho, Yong Song ^b   Kim, Yoon Keun ^b   Hwang, Hyung Ju ^b  

^a Konkuk University   (South Korea)

^b Pohang University of Science and Technology (POSTECH)   (South Korea)

^c UNIVERSITY OF LEEDS   (United Kingdom)

Author keywords

Asthma; Inammation; LPS; Microenvironment; Th1 Th2 cells

Indexed keywords

CYTOKINE;

ARTICLE; ASTHMA; BIOLOGICAL MODEL; COMPUTER SIMULATION; HUMAN; IMMUNOLOGY; TH1 CELL; TH2 CELL;

ASTHMA; COMPUTER SIMULATION; CYTOKINES; HUMANS; MODELS, IMMUNOLOGICAL; TH1 CELLS; TH2 CELLS;

EID: 84884482424     PISSN: 15471063     EISSN: 15510018     Source Type: Journal    
DOI: 10.3934/mbe.2013.10.1095     Document Type: Article

References (114)

1. R. Abe, S. Donnelly, T. Peng, R. Bucala and C. Metz, Peripheral blood fibrocytes: differen-tiation pathway and migration to wound sites, J. Immunol., 166 (2001), 7556-7562. (Pubitemid 32525636)
2. O. Akbari, G. Freeman, E. Meyer, E. Greenfield, T. Chang, A. Sharpe, G. Berry, R. DeKruyff and D. Umetsu, Antigen-specific regulatory T cells develop via the ICOS-ICOS-ligand path-way and inhibit allergen-induced airway hyperreactivity, Nat. Med., 8 (2002), 1024-1032. (Pubitemid 35033708)
3. C. A. Akdis, T. Blesken, M. Akdis, B. Wüthrich and K. Blaser, Role of interleukin 10 in specific immunotherapy, J. Clin. Invest., 102 (1998), 98-106. (Pubitemid 28323835)
4. M. Akdis and C. A. Akdis, Mechanisms of allergen-specific immunotherapy, J. Allergy Clin. Immunol., 119 (2007), 780-791.
5. T. Alarcón, H. Byrne and P. Maini, Towards whole-organ modelling of tumour growth, Prog. Biophys. Mol. Biol., 85 (2004), 451-472. (Pubitemid 38629922)
6. H17 cells in asthma and COPD, Annu. Rev. Physiol., 72 (2010), 495-516.
7. D. Amsen, A. Antov, D. Jankovic, A. Sher, F. Radtke, A. Souabni, M. Busslinger, B. Mc-Cright, T. Gridley and R. Flavell, Direct regulation of Gata3 expression determines the T helper differentiation potential of Notch, Immunity, 27 (2007), 89-99. (Pubitemid 47096801)
8. F. Annunziato, L. Cosmi and S. Romagnani, Human and murine Th17, Curr. Opin. HIV AIDS, 5 (2010), 114-119.
9. P. Barnes, Th2 cytokines and asthma: An introduction, Respir. Res., 2 (2001), 64-65. (Pubitemid 34187908)
10. R. L. Baror and L. Segel, On the role of a possible dialogue between cytokine and TCR-presentation mechanisms in the regulation of autoimmune disease, J. Theor. Biol., 190 (1998), 161-178. (Pubitemid 28108034)
11. U. Behn, H. Dambeck and G. Metzner, Modeling Th1-Th2 regulation, allergy, and hy-posensitization, in "Dynamical Modeling In Biotechnology," Lectures Presented at the EU Advanced Workshop, Universität Leipzig NTZ 48/1997, World Scientific, Singapore, (2000), 227-243.
12. M. Berry, C. Brightling, I. Pavord and A. Wardlaw, TNF-alpha in asthma, Curr. Opin. Pharmacol., 7 (2007), 279-282.
13. B. Bochner, B. Undem and L. Lichtenstein, Immunological aspects of allergic asthma, Annu. Rev. Immunol., 12 (1994), 295-335. (Pubitemid 24140417)
14. A. Bolinger and M. Taeubel, Recombinant interferon gamma for treatment of chronic gran-ulomatous disease and other disorders, Clin. Pharm., 11 (1992), 834-850.
15. T. Bongartz, A. Sutton, M. Sweeting, I. Buchan, E. Matteson and V. Montori, Anti-TNF antibody therapy in rheumatoid arthritis and the risk of serious infections and malignancies: Systematic review and meta-analysis of rare harmful effects in randomized controlled trials, JAMA, 295 (2006), 2275-2285. (Pubitemid 43736578)
16. L. Borish, H. Nelson, M. Lanz, L. Claussen, J. Whitmore, J. Agosti and L. Garrison, Interleukin-4 receptor in moderate atopic asthma. A phase I/II randomized, placebo-controlled trial, Am. J. Respir. Crit. Care Med., 160 (1999), 1816-1823. (Pubitemid 30004681)
17. D. Bray, "Cell Movements: From Molecules to Motility," Garland Pub., 2000.
18. T. Brocker, Survival of mature CD4 T lymphocytes is dependent on major histocompatibility complex class II-expressing dendritic cells, J. Exp. Med., 186 (1997), 1223-1232. (Pubitemid 27469017)
19. R. Callard and A. Yates, Immunology and mathematics: Crossing the divide, Immunology, 115 (2005), 21-33. (Pubitemid 40593288)
20. J. Carneiro, J. Stewart, A. Coutinho and G. Coutinho, The ontogeny of class-regulation of CD4+T lymphocte populations, Int. Immunol., 7 (1995), 1265-1277.
21. S. Cho, L. Stanciu, S. Holgate and S. Johnston, Increased interleukin-4, interleukin-5, and interferon-gamma in airway CD4+ and CD8+ T cells in atopic asthma, Am. J. Respir. Crit. Care Med., 171 (2005), 224-230.
22. D. Coombs and B. Goldstein, Effects of the geometry of the immunological synapse on the delivery of effector molecules, Biophys. J., 87 (2004), 2215-2220. (Pubitemid 41071324)
23. L. Cosmi, F. Liotta, E. Maggi, S. Romagnani and F. Annunziato, Th17 cells: New players in asthma pathogenesis, Allergy, 66 (2011), 989-998.
24. L. Cosmi, L. Maggi, V. Santarlasci, M. Capone, E. Cardilicchia and F. F. et al., Identification of a novel subset of human circulating memory CD4(+) T cells that produce both IL-17A and IL-4, J. Allergy Clin. Immunol., 125 (2010), 222-230.
25. E. Cutz, H. Levison and D. Cooper, Ultrastructure of airways in children with asthma, Histopathology, 2 (1978), 407-421. (Pubitemid 9041198)
26. E. Deenick, A. Gett and P. Hodgkin, Stochastic model of T cell proliferation: A calculus revealing IL-2 regulation of precursor frequencies, cell cycle time, and survival, J. Immunol., 170 (2003), 4963-4972. (Pubitemid 36554725)
27. T. Demuth, N. Hopf, O. Kempski, D. Sauner, M. Herr, A. Giese and A. Perneczky, Migratory activity of human glioma cell lines in vitro assessed by continuous single cell observation, Clin. Exp. Metastasis, 18 (2000), 589-597. (Pubitemid 32964321)
28. T. V. Dyke, A. Reilly and R. Genco, Regression line analysis of neutrophil chemotaxis, Immunopharmacology, 4 (1982), 23-39. (Pubitemid 12110039)
29. S. Eisenbarth, D. Piggott, J. Huleatt, I. Visintin, C. Herrick and K. Bottomly, Lipopolysaccharide-enhanced, toll-like receptor 4-dependent T helper cell type 2 responses to inhaled antigen, J. Exp. Med., 196 (2002), 1645-1651. (Pubitemid 36026476)
30. M. Fishman and A. Perelson, Modeling T cell-antigen presenting cell interactions, J. Theor. Biol., 160 (1993), 311-342.
31. M. Fishman and A. Perelson, Th1/2 cross-regulation, J. Theor. Biol., 170 (1994), 25-56.
32. M. Fishman and A. Perelson, Th1/Th2 differentiation and cross regulation, Bull. Math. Biol., 61 (1999), 403-436.
33. K. Francis and B. Palsson, Effective intercellular communication distances are determined by the relative time constants for cyto/chemokine secretion and diffusion, Proc. Natl. Acad. Sci. USA, 94 (1997), 12258-12262. (Pubitemid 27492515)
34. J. Gao, Q. Xue, C. Papasian and D. Morrison, Bacterial DNA and lipopolysaccharide in-duce synergistic production of TNF-alpha through a post-transcriptional mechanism, J. Immunol., 166 (2001), 6855-6860. (Pubitemid 32467231)
35. J. Gereda, D. Leung, A. Thatayatikom, J. Streib, M. Price, M. Klinnert and A. Liu, Relation between house-dust endotoxin exposure, type 1 T-cell development, and allergen sensitisation in infants at high risk of asthma, Lancet., 355 (2000), 1680-1683. (Pubitemid 30248480)
36. A. Gett and P. Hodgkin, A cellular calculus for signal integration by T cells, Nat. Immunol., 1 (2000), 239-244.
37. J. Glasgow, B. Farrell, E. Fisher, D. Lauffenburger and R. Daniele, The motile response of alveolar macrophages. an experimental study using single-cell and cell population ap-proaches, Am. Rev. Respir. Dis., 139 (1989), 320-329. (Pubitemid 19057403)
38. F. Groß, G. Metznerb and U. Behn, Mathematical modelling of allergy and specific im-munotherapy: Th1-Th2-Treg interactions, J. Theor. Biol., 269 (2011), 70-78.
39. G. Grunig, M. Warnock, A. Wakil, R. Venkayya, F. Brombacher, D. Rennick, D. Sheppard, M. Mohrs, D. Donaldson, R. Locksley and D. Corry, Requirement for IL-13 independently of IL-4 in experimental asthma, Science, 282 (1998), 2261-2263. (Pubitemid 29004075)
40. H. Gudmundsdottir, A. Wells and L. Turka, Dynamics and requirements of T cell clonal expansion in vivo at the single-cell level: effector function is linked to proliferative capacity, J. Immunol., 162 (1999), 5212-5223. (Pubitemid 29307126)
41. Q. Hamid and M. Tulic, Immunobiology of asthma, Annu. Rev. Physiol., 71 (2009), 489-507.
42. M. Harber, A. Sundstedt and D. Wraith, The role of cytokines in immunological tolerance: potential for therapy, Expert. Rev. Mol. Med., 2 (2000), 1-20.
43. B. Hegedus, J. Zach, A. Czirok, J. Lovey and T. Vicsek, Irradiation and taxol treatment result in non-monotonous, dose-dependent changes in the motility of glioblastoma cells, J. Neurooncol., 67 (2004), 147-157. (Pubitemid 38418263)
44. S. Herrmann, G. Winter, S. Mohl, F. Siepmann and J. Siepmann, Mechanisms controlling protein release from lipidic implants: Effects of peg addition, Journal of Controlled Release, 118 (2007), 161-168. (Pubitemid 46343669)
45. P. Howarth, K. Babu, H. Arshad, L. Lau, M. Buckley, W. McConnell, P. Beckett, M. Ali, A. Chauhan, S. Wilson, A. Reynolds, D. Davies and S. Holgate, Tumour necrosis factor (TNF alpha) as a novel therapeutic target in symptomatic corticosteroid dependent asthma, Thorax, 60 (2005), 1012-1018. (Pubitemid 41705469)
46. A. Jansson, M. Fagerlind, D. Karlsson, P. Nilsson and M. Cooley, In silico simulations suggest that Th-cell development is regulated by both selective and instructive mechanisms, Immunol. Cell Biol., 84 (2006), 218-226.
47. A. Jansson, M. Harlen, S. Karlsson, P. Nilsson and M. Cooley, 3D computation modelling of the inuence of cytokine secretion on Th-cell development suggests that negative selection (inhibition of Th1 cells) is more effective than positive selection by IL-4 for Th2 cell dominance modelling Th cell selection, Immunology and Cell Biology, 85 (2007), 189-196. (Pubitemid 46701424)
48. S. Jeon, S. Oh, H. Park, Y. Kim, E. Shim, H. Lee, M. Oh, B. Bang, E. Chun, S. Kim, Y. Gho, Z. Zhu, Y. Kim and Y. Kim, TH2 and TH1 lung inammation induced by airway allergen sensitization with low and high doses of double-stranded RNA, J. Allergy Clin. Immunol., 120 (2007), 803-812. (Pubitemid 47531833)
49. T. Katakai, K. Mori, T. Masuda and A. Shimizu, Differential localization of Th1 and Th2 cells in autoimmune gastritis, Int. Immunol., 10 (1998), 1325-1334. (Pubitemid 28414338)
50. Y. Kim and A. Friedman, Interaction of tumor with its microenvironment : A mathematical model, Bull. Math. Biol., 72 (2010), 1029-1068.
51. Y. Kim, S. Lawler, M. Nowicki, E. Chiocca and A. Friedman, A mathematical model of brain tumor: Pattern formation of glioma cells outside the tumor spheroid core, J. Theo. Biol., 260 (2009), 359-371.
52. Y. Kim and S. Lim, The role of the microenvironment in tumor invasion,2009 Proceedings of the Fourth SIAM Conference on Mathematics for Industry (MI09), (2010), 84-92.
53. Y. Kim, S. Oh, S. Jeon, H. Park, S. Lee, E. Chun, B. Bang, H. Lee, M. Oh, Y. Kim, J. Kim, Y. Gho, S. Cho, K. Min, Y. Kim and Z. Zhu, Airway exposure levels of lipopolysaccharide determine type 1 versus type 2 experimental asthma, J. Immunol., 178 (2007), 5375-5382. (Pubitemid 46595324)
54. Y. Kim, M. Stolarska and H. Othmer, The role of the microenvironment in tumor growth and invasion, Progress in Biophysics and Molecular Biology, 106 (2011), 353-379.
55. Y. Kim, J. C. S.W. Hong, T. Shin, H. Moon and E. C. et al., Vascular endothelial growth factor is a key mediator in the development of T cell priming and its polarization to type 1 and type 17 T helper cells in the airways, J. Immunol., 183 (2009), 5113-5120.
56. Y. Kim, J. Wallace, F. Li, M. Ostrowski and A. Friedman, Transformed epithelial cells and fibroblasts/myofibroblasts interaction in breast tumor: a mathematical model and experiments, J. Math. Biol., 61 (2010), 401-421.
57. J. Kirberg, A. Berns and H. Boehmer, Peripheral T cell survival requires continual ligation of the T cell receptor to major histocompatibility complexencoded molecules, J. Exp. Med., 186 (1997), 1269-1275. (Pubitemid 27469022)
58. D. Kirschner and J. Panetta, Modeling immunotherapy of the tumor-immune interaction, J. Math. Biol., 37 (1998), 235-252.
59. L. Kreuz and A. Levy, Physical properties of chick interferon, J. Bacteriology, 89 (1965), 462-469.
60. H. Kuipers, D. Hijdra, V. Vries, H. Hammad, J. Prins, A. Coyle, H. Hoogsteden and B. Lambrecht, Lipopolysaccharide-induced suppression of airway Th2 responses does not require IL-12 production by dendritic cells, J. Immunol., 171 (2003), 3645-3654. (Pubitemid 37254568)
61. R. Kumar, D. Webb, C. Herbert and P. Foster, Interferon-gamma as a possible target in chronic asthma, Inamm. Allergy Drug Targets, 5 (2006), 253-256. (Pubitemid 44941936)
62. C. Langrish, Y. Chen., W. M. Blumenschein, J. Mattson, B. Basham, J. Sedgwick, T. Mc-Clanahan, R. Kastelein and D. Cua, Il-23 drives a pathogenic T cell population that induces autoimmune inammation, J. Exp. Med., 201 (2005), 233-240. (Pubitemid 40189432)
63. Y. Lee, H. Turner, C. Maynard, J. Oliver, D. Chen, C. Elson and C. Weaver, Late developmental plasticity in the T helper 17 lineage, Immunity, 30 (2009), 92-107.
64. C. M. Lloyd and C. M. Hawrylowicz, Regulatory T cells in asthma, Immunity, 31 (2009), 438-449.
65. H. Lortat-Jacob, F. Baltzer and J. Grimaud, Heparin decreases the blood clearance of interferon-gamma and increases its activity by limiting the processing of its carboxyl-terminal sequence, The Journal of Biological Chemistry, 271 (1996), 16139-16143. (Pubitemid 26236230)
66. G. Lugo-Villarino, R. Maldonado-Lopez, R. Possemato, C. Penaranda and L. Glimcher, T-bet is required for optimal production of IFN-gamma and antigen-specifict cell activation by dendritic cells, Proc. Natl. Acad. Sci. USA, 100 (2003), 7749-7754. (Pubitemid 36760041)
67. A. Magnan, L. Mély, C. Camilla, M. Badier, F. Montero-Julian, C. Guillot, B. Casano, S. Prato, V. Fert, P. Bongrand and D. Vervloet, Assessment of the Th1/Th2 paradigm in whole blood in atopy and asthma. Increased IFN-gamma-producing CD8(+) T cells in asthma, Am. J. Respir. Crit. Care Med., 161 (2000), 1790-1796. (Pubitemid 30418109)
68. S. Marino, I. Hogue, C. Ray and D. Kirschner, A methodology for performing global uncer-tainty and sensitivity analysis in systems biology, J. Theor. Biol., 254 (2008), 178-196.
69. M. Masoli, D. Fabian, S. Holt and R. Beasley, The global burden of asthma: Executive summary of the GINA dissemination committee report, Allergy, 59 (2004), 469-478. (Pubitemid 38580764)
70. G. Mazzarella, A. Bianco, E. Catena, R. De Palma and G. Abbate, Th1/Th2 lymphocyte polarization in asthma, Allergy, 55 (2000), 6-9. (Pubitemid 30430371)
71. O. Michel, R. Ginanni, J. Duchateau, F. Vertongen, B. Bon and R. Sergysels, Domestic endotoxin exposure and clinical severity of asthma, Clin. Exp. Allergy, 21 (1991), 441-448.
72. M. Miller, S. Wei, I. Parker and M. Cahalan, Two-photon imaging of lymphocyte motility and antigen response in intact lymph node, Science, 296 (2002), 1869-1873. (Pubitemid 34596273)
73. H.-G. Moon, Y.-M. Tae, Y.-S. Kim, S. Gyu Jeon, S.-Y. Oh, Y. Song Gho, Z. Zhu and Y.-K. Kim, Conversion of Th17-type into Th2-type inammation by acetyl salicylic acid via the adenosine and uric acid pathway in the lung, Allergy, 65 (2010), 1093-1103.
74. B. Morel, J. Kalagnanam and P. Morel, Mathematical modelling of Th1-Th2 dynamics, in "Theoretical and Experimental Insights into Immunology" (eds. A. S. Perelson and G. Weisbuch), chapter H66 Nato ASI, Springer-Verlag, Berlin, Germany, (1992), 171-189.
75. J. Morjaria, K. Babu, S. Holgate and R. Polosa, Tumour necrosis factor-alpha as a thera-peutic target in asthma, Drug Discovery Today: Therapeutic Strategies, 3 (2006), 309-316. (Pubitemid 44793685)
76. J. Morjaria, K. Babu, R. Polosa and S. Holgate, Tumour necrosis factor-alpha in severe corticosteroid-refractory asthma, Exp. Rev. Resp. Med., 1 (2007), 51-63.
77. T. Mosmann, H. Cherwinski, M. Bond, M. Giedlin and R. Coffman, Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins, J. Immunol., 136 (1986), 2348-2357. (Pubitemid 16136806)
78. T. Mosmann and R. Coffman, TH1 and TH2 cells: Different patterns of lymphokine secretion lead to different functional properties, Annu. Rev. Immunol., 7 (1989), 145-173. (Pubitemid 19138011)
79. E. Muraille, O. Leo and M. Kaufman, The role of antigen presentation in the regulation of class-specific (Th1/Th2) immune responses, J. Biol. Syst., 3 (1995), 397-408.
80. A. Murphy, "Asthma in Focus," In Focus Series, Pharmaceutical Press, 2007.
81. K. Murphy, P. Travers and M. Walport, "Janeway's Immunobiology," 7th edition, Garland Science Publishing, New York, 2007.
82. L. Narhi, J. Philo, T. Li, M. Zhang, B. Samal and T. Arakawa, Induction of alpha-helix in the beta-sheet protein tumor necrosis factor-alpha: Acid-induced denaturation, Biochemistry, 35 (1996), 11454-11460. (Pubitemid 26299320)
83. D. Nesic and S. Vukmanovic, MHC class I is required for peripheral accumulation of CD8+ thymic emigrants, J. Immunol., 160 (1998), 3705-3712. (Pubitemid 28176071)
84. S. Olenchock, J. May, D. Pratt and P. Morey, Occupational exposures to airborne endotoxins in agriculture, Prog. Clin. Biol. Res., 231 (1987), 475-487.
85. J. Oliver, L. Bland, C. Oettinger, M. Arduino, S. McAllister, S. Aguero and M. Favero, Cytokine kinetics in an in vitro whole blood model following an endotoxin challenge, Lymphokine Cytokine Res., 12 (1993), 115-120. (Pubitemid 23141784)
86. G. J. Pettet, H. M. Byrne, D. L. S. Mcelwain and J. Norbury, A model of wound-healing angiogenesis in soft tissue, Math. Bios., 136 (1996), 35-63. (Pubitemid 26251007)
87. A. Ray, A. Khare, N. Krishnamoorthy, Z. Qi and P. Ray, Regulatory T cells in many avors control asthma, Mucosal. Immunol., 3 (2010), 216-229.
88. J. Richter, G. Metzner and U. Behn, Mathematical modelling of venom immunotherapy, Journal of Theoretical Medicine, 4 (2002), 119-132. (Pubitemid 34823469)
89. D. S. Robinson, Regulatory T cells and asthma, Clin. Exp. Allergy., 39 (2009), 1314-1323.
90. R. Rooke, C.Waltzinger, C. Benoist and D. Mathis, Targeted complementation of MHC class II defficiency by intrathymic delivery of recombinant adenoviruses, Immunity, 7 (1997), 123-134. (Pubitemid 27357270)
91. C. Ruedl, M. Bachmann and M. Kopf, The antigen dose determines t helper subset devel-opment by regulation of CD40 ligand, Eur. J. Immunol., 30 (2000), 2056-2064. (Pubitemid 30456202)
92. S. Sakaguchi, Regulatory T cells: Key controllers of immunologic self-tolerance, Cell, 101 (2000), 455-458.
93. J. Scheel, S. Weimans, A. Thiemann, E. Heisler and M. Hermann, Exposure of the murine RAW 264.7 macrophage cell line to hydroxyapatite dispersions of various composition and morphology: Assessment of cytotoxicity, activation and stress response, Toxicol. in Vitro, 23 (2009), 531-538.
94. A. Schwingshackl, M. Duszyk, N. Brown and R. Moqbel, Human eosinophils release matrix metalloproteinase-9 on stimulation with TNF-alpha, J. Allergy Clin. Immunol., 104 (1999), 983-990. (Pubitemid 29532119)
95. D. Stickle, D. Lauffenburger and R. Daniele, The motile response of lung macrophages: Theoretical and experimental approaches using the linear under-agarose assay, J. Leukoc. Biol., 38 (1985), 383-401. (Pubitemid 15000664)
96. C. L. Stokes and D. A. Lauffenburger, Analysis of the roles of microvessel endothelial cell random motility and chemotaxis in angiogenesis, J. Theor. Biol., 152 (1991), 377-403.
97. E. Suzuki, A. Tsutsumi, D. Goto, I. Matsumoto, S. Ito, M. Otsu, M. Onodera, S. Takahashi, Y. Sato and T. Sumida, Gene transduction of tristetraprolin or its active domain reduces TNF-alpha production by Jurkat T cells, Int. J. Mol. Med., 17 (2006), 801-809.
98. M. Swanson, W. Lee and V. Sanders, IFN-gamma production by Th1 cells generated from naive CD4+ T cells exposed to norepinephrine, J. Immunol., 166 (2001), 232-240. (Pubitemid 32038437)
99. S. Takeda, H. Rodewald, H. Arakawa, H. Bluethmann and T. Shimizu, MHC class II molecules are not required for survival of newly generated CD4+ T cells, but affect their long-term life span, Immunity, 5 (1996), 217-228. (Pubitemid 26341365)
100. R. Tyson, L. Stern and R. LeVeque, Fractional step methods applied to a chemotaxis model, J. Math. Biol., 41 (2000), 455-475.
101. R. Vogel and U. Behn, Th1-Th2 regulation and allergy: Bifurcation analysis of the non-autonomous system, in "Mathematical Modeling of Biological Systems," Volume II (eds. A. Deutsch, R. Parra, R. J. de Boer, O. Diekmann, P. Jagers, E. Kisdi, M. Kretzschmar, P. Lansky, and H. Metz), Modeling and Simulation in Science, Engineering and Technology, Birkhäuser Boston, (2008), 145-155.
102. Y. Wan, Multi-tasking of helper T cells, Immunology, 130 (2010), 166-171.
103. 2 memory/effector cells that produce inammatory IL-17 cytokine and promote the exacerbation of chronic allergic asthma, J. Exp. Med., 207 (2010), 2479-2491.
104. M. Wills-Karp, J. Luyimbazi, X. Xu, B. Schofield, T. Neben, C. Karp and D. Donaldson, Interleukin-13: Central mediator of allergic asthma, Science, 282 (1998), 2258-2261. (Pubitemid 29004074)
105. M. Wills-Karp, J. Santeliz and C. L. Karp, The germless theory of allergic disease: Revisiting the hygiene hypothesis, Nat. Rev. Immunol., 1 (2001), 69-75. (Pubitemid 33741977)
106. D. Witherden, N. van Oers, C.Waltzinger, A.Weiss, C. Benoist and D. Mathis, Tetracycline-controllable selection of CD4(+) T cells: Half-life and survival signals in the absence of major histocompatibility complex class II molecules, J. Exp. Med., 191 (2000), 355-364. (Pubitemid 30060924)
107. M. Yang, R. Kumar and P. Foster, Interferon-gamma and pulmonary macrophages con-tribute to the mechanisms underlying prolonged airway hyperresponsiveness, Clin. Exp. Allergy, 40 (2010), 163-173.
108. Y. Yang, H.-L. Zhang and J. Wu, Role of T regulatory cells in the pathogenesis of asthma, Chest., 138 (2010), 1282-1283.
109. A. Yates, C. Bergmann, J. V. Hemmen, J. Stark and R. Callard, Cytokine-modulated regu-lation of helper T cell populations, J. Theor. Biol., 206 (2000), 539-560.
110. A. Yates, R. Callard and J. Stark, Combining cytokine signalling with T-bet and GATA-3 regulation in Th1 and Th2 differentiation: A model for cellular decision-making, J. Theor. Biol., 231 (2004), 181-196. (Pubitemid 39221871)
111. M. Yazdanbakhsh, P. G. Kremsner and R. van Ree, Allergy, parasites, and the hygiene hypothesis, Science, 296 (2002), 490-494.
112. Y. Zhao, J. Yang, Y. Gao and W. Guo, Th17 immunity in patients with allergic asthma, Int. Arch. Allergy Immunol., 151 (2010), 297-307.
113. L. Zhou, I. Ivanov, R. Spolski, R. Min, K. Shenderov, T. Egawa, D. Levy, W. Leonard and D. Littman, IL-6 programs T(H)-17 cell differentiation by promoting sequential engagement of the IL-21 and IL-23 pathways, Nat. Immunol., 8 (2007), 967-974. (Pubitemid 47300011)
114. J. Zhuang and G. Wogan, Growth and viability of macrophages continuously stimulated to produce nitric oxide, Proc. Natl. Acad. Sci. USA, 94 (1997), 11875-11880. (Pubitemid 27467810)