{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T06:21:51Z","timestamp":1783578111865,"version":"3.55.0"},"publisher-location":"Cham","reference-count":45,"publisher":"Springer International Publishing","isbn-type":[{"value":"9783319124179","type":"print"},{"value":"9783319124186","type":"electronic"}],"license":[{"start":{"date-parts":[[2014,1,1]],"date-time":"2014-01-01T00:00:00Z","timestamp":1388534400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014]]},"DOI":"10.1007\/978-3-319-12418-6_16","type":"book-chapter","created":{"date-parts":[[2014,10,23]],"date-time":"2014-10-23T15:39:37Z","timestamp":1414078777000},"page":"123-134","source":"Crossref","is-referenced-by-count":9,"title":["Multi-scale Simulation of T Helper Lymphocyte Differentiation"],"prefix":"10.1007","author":[{"given":"P.","family":"Tieri","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V.","family":"Prana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Colombo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Santoni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Castiglione","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","reference":[{"key":"16_CR1","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1152\/advan.00066.2013","volume":"37","author":"N.D. Pennock","year":"2013","unstructured":"Pennock, N.D., White, J.T., Cross, E.W., Cheney, E.E., Tamburini, B.A., Kedl, R.M.: T cell responses: naive to memory and everything in between. Adv. Physiol. Educ.\u00a037, 273\u2013283 (2013)","journal-title":"Adv. Physiol. Educ."},{"key":"16_CR2","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1146\/annurev-immunol-030409-101212","volume":"28","author":"J. Zhu","year":"2010","unstructured":"Zhu, J., Yamane, H., Paul, W.E.: Differentiation of effector CD4 T cell populations (*). Annu. Rev. Immunol.\u00a028, 445\u2013489 (2010)","journal-title":"Annu. Rev. Immunol."},{"key":"16_CR3","doi-asserted-by":"publisher","first-page":"9364","DOI":"10.1073\/pnas.142284699","volume":"99","author":"T. Hofer","year":"2002","unstructured":"Hofer, T., Nathansen, H., Lohning, M., Radbruch, A., Heinrich, R.: GATA-3 transcriptional imprinting in Th2 lymphocytes: a mathematical model. Proc. Natl. Acad. Sci. U.S.A.\u00a099, 9364\u20139368 (2002)","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"16_CR4","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1016\/j.jtbi.2004.06.013","volume":"231","author":"A. Yates","year":"2004","unstructured":"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.\u00a0231, 181\u2013196 (2004)","journal-title":"J. Theor. Biol."},{"key":"16_CR5","doi-asserted-by":"crossref","unstructured":"Hong, T., Xing, J., Li, L., Tyson, J.J.: A mathematical model for the reciprocal differentiation of T helper 17 cells and induced regulatory T cells. PLoS Comput. Biol. 7, e1002122 (2011)","DOI":"10.1371\/journal.pcbi.1002122"},{"key":"16_CR6","doi-asserted-by":"crossref","unstructured":"Carbo, A., Hontecillas, R., Kronsteiner, B., Viladomiu, M., Pedragosa, M., Lu, P., Philipson, C.W., Hoops, S., Marathe, M., Eubank, S., Bisset, K., Wendelsdorf, K., Jarrah, A., Mei, Y., Bassaganya-Riera, J.: Systems modeling of molecular mechanisms controlling cytokine-driven CD4+ T cell differentiation and phenotype plasticity. PLoS Comput. Biol. 9, e1003027 (2013)","DOI":"10.1371\/journal.pcbi.1003027"},{"key":"16_CR7","doi-asserted-by":"crossref","unstructured":"Naldi, A., Carneiro, J., Chaouiya, C., Thieffry, D.: Diversity and plasticity of Th cell types predicted from regulatory network modelling. PLoS Comput. Biol. 6, e1000912 (2010)","DOI":"10.1371\/journal.pcbi.1000912"},{"key":"16_CR8","doi-asserted-by":"crossref","unstructured":"Carbo, A., Hontecillas, R., Andrew, T., Eden, K., Mei, Y., Hoops, S., Bassaganya-Riera, J.: Computational modeling of heterogeneity and function of CD4+ T cells. Frontiers in Cell and Developmental Biology\u00a02 (2014)","DOI":"10.3389\/fcell.2014.00031"},{"key":"16_CR9","doi-asserted-by":"crossref","first-page":"2348","DOI":"10.4049\/jimmunol.136.7.2348","volume":"136","author":"T.R. Mosmann","year":"1986","unstructured":"Mosmann, T.R., Cherwinski, H., Bond, M.W., Giedlin, M.A., Coffman, R.L.: Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J. Immunol.\u00a0136, 2348\u20132357 (1986)","journal-title":"J. Immunol."},{"key":"16_CR10","doi-asserted-by":"publisher","first-page":"1910","DOI":"10.1074\/jbc.M207577200","volume":"278","author":"S. Aggarwal","year":"2003","unstructured":"Aggarwal, S., Ghilardi, N., Xie, M.-H., de Sauvage, F.J., Gurney, A.L.: Interleukin-23 promotes a distinct CD4 T cell activation state characterized by the production of interleukin-17. J. Biol. Chem.\u00a0278, 1910\u20131914 (2003)","journal-title":"J. Biol. Chem."},{"key":"16_CR11","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.4049\/jimmunol.155.3.1151","volume":"155","author":"S. Sakaguchi","year":"1995","unstructured":"Sakaguchi, S., Sakaguchi, N., Asano, M., Itoh, M., Toda, M.: 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.\u00a0155, 1151\u20131164 (1995)","journal-title":"J. Immunol."},{"key":"16_CR12","doi-asserted-by":"publisher","first-page":"1105","DOI":"10.1093\/intimm\/dxp095","volume":"21","author":"S. Sakaguchi","year":"2009","unstructured":"Sakaguchi, S., Wing, K., Onishi, Y., Prieto-Martin, P., Yamaguchi, T.: Regulatory T cells: how do they suppress immune responses? Int. Immunol.\u00a021, 1105\u20131111 (2009)","journal-title":"Int. Immunol."},{"key":"16_CR13","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1016\/j.it.2013.07.006","volume":"34","author":"K.P. Walsh","year":"2013","unstructured":"Walsh, K.P., Mills, K.H.: Dendritic cells and other innate determinants of T helper cell polarisation. Trends Immunol.\u00a034, 521\u2013530 (2013)","journal-title":"Trends Immunol."},{"key":"16_CR14","doi-asserted-by":"publisher","first-page":"655","DOI":"10.1016\/S0092-8674(00)80702-3","volume":"100","author":"S.J. Szabo","year":"2000","unstructured":"Szabo, S.J., Kim, S.T., Costa, G.L., Zhang, X., Fathman, C.G., Glimcher, L.H.: A novel transcription factor, T-bet, directs Th1 lineage commitment. Cell\u00a0100, 655\u2013669 (2000)","journal-title":"Cell"},{"key":"16_CR15","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1016\/j.coi.2012.06.003","volume":"24","author":"R.M. Maizels","year":"2012","unstructured":"Maizels, R.M., Hewitson, J.P., Smith, K.A.: Susceptibility and immunity to helminth parasites. Curr. Opin. Immunol.\u00a024, 459\u2013466 (2012)","journal-title":"Curr. Opin. Immunol."},{"key":"16_CR16","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1016\/j.coi.2007.04.005","volume":"19","author":"B. Stockinger","year":"2007","unstructured":"Stockinger, B., Veldhoen, M.: Differentiation and function of Th17 T cells. Curr. Opin. Immunol.\u00a019, 281\u2013286 (2007)","journal-title":"Curr. Opin. Immunol."},{"key":"16_CR17","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1007\/s12064-010-0112-x","volume":"129","author":"L. Mendoza","year":"2010","unstructured":"Mendoza, L., Pardo, F.: A robust model to describe the differentiation of T-helper cells. Theory Biosci.\u00a0129, 283\u2013293 (2010)","journal-title":"Theory Biosci."},{"key":"16_CR18","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/j.cellimm.2006.12.006","volume":"244","author":"V. Baldazzi","year":"2006","unstructured":"Baldazzi, V., Castiglione, F., Bernaschi, M.: An enhanced agent based model of the immune system response. Cell Immunol.\u00a0244, 77\u201379 (2006)","journal-title":"Cell Immunol."},{"key":"16_CR19","unstructured":"Neumann, J.V.: Theory of Self-Reproducing Automata. University of Illinois Press (1966)"},{"key":"16_CR20","unstructured":"Burnet, F.M.: The Nobel Lectures in Immunology. The Nobel Prize for Physiology or Medicine, 1960. Immunologic recognition of self. Scand. J. Immunol. 33, 3\u201313 (1991)"},{"key":"16_CR21","doi-asserted-by":"publisher","first-page":"1649","DOI":"10.1126\/science.129.3364.1649","volume":"129","author":"J. Lederberg","year":"1959","unstructured":"Lederberg, J.: Genes and antibodies. Science\u00a0129, 1649\u20131653 (1959)","journal-title":"Science"},{"key":"16_CR22","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1038\/211242a0","volume":"211","author":"S. Brenner","year":"1966","unstructured":"Brenner, S., Milstein, C.: Origin of antibody variation. Nature\u00a0211, 242\u2013243 (1966)","journal-title":"Nature"},{"key":"16_CR23","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1016\/0014-4827(61)90192-6","volume":"25","author":"L. Hayflick","year":"1961","unstructured":"Hayflick, L., Moorhead, P.S.: The serial cultivation of human diploid cell strains. Exp. Cell Res.\u00a025, 585\u2013621 (1961)","journal-title":"Exp. Cell Res."},{"key":"16_CR24","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1146\/annurev.immunol.21.120601.141110","volume":"21","author":"R.H. Schwartz","year":"2003","unstructured":"Schwartz, R.H.: T cell anergy. Annu. Rev. Immunol.\u00a021, 305\u2013334 (2003)","journal-title":"Annu. Rev. Immunol."},{"key":"16_CR25","doi-asserted-by":"publisher","first-page":"1602","DOI":"10.1073\/pnas.77.3.1602","volume":"77","author":"G.J. Nossal","year":"1980","unstructured":"Nossal, G.J., Pike, B.L.: Clonal anergy: persistence in tolerant mice of antigen-binding B lymphocytes incapable of responding to antigen or mitogen. Proc. Natl. Acad. Sci. U.S.A.\u00a077, 1602\u20131606 (1980)","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"16_CR26","doi-asserted-by":"publisher","first-page":"991","DOI":"10.1146\/annurev.iy.12.040194.005015","volume":"12","author":"P. Matzinger","year":"1994","unstructured":"Matzinger, P.: Tolerance, danger, and the extended family. Annu. Rev. Immunol.\u00a012, 991\u20131045 (1994)","journal-title":"Annu. Rev. Immunol."},{"key":"16_CR27","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1126\/science.1071059","volume":"296","author":"P. Matzinger","year":"2002","unstructured":"Matzinger, P.: The danger model: a renewed sense of self. Science\u00a0296, 301\u2013305 (2002)","journal-title":"Science"},{"key":"16_CR28","unstructured":"Jerne, N.: Towards a network theory of the immune system. Ann Immunol. 125C, 373\u2013389 (1974)"},{"key":"16_CR29","doi-asserted-by":"crossref","unstructured":"Welsh, R.M., Selin, L.K.: Attrition of memory CD8 T cells. Nature 459, E3-4; discussion E4 (2009)","DOI":"10.1038\/nature08091"},{"key":"16_CR30","doi-asserted-by":"publisher","first-page":"4284","DOI":"10.4049\/jimmunol.176.7.4284","volume":"176","author":"K. Bahl","year":"2006","unstructured":"Bahl, K., Kim, S.-K., Calcagno, C., Ghersi, D., Puzone, R., Celada, F., Selin, L.K., Welsh, R.M.: IFN-induced attrition of CD8 T cells in the presence or absence of cognate antigen during the early stages of viral infections. J. Immunol.\u00a0176, 4284\u20134295 (2006)","journal-title":"J. Immunol."},{"key":"16_CR31","doi-asserted-by":"publisher","first-page":"3350","DOI":"10.1093\/bioinformatics\/btm408","volume":"23","author":"F. Castiglione","year":"2007","unstructured":"Castiglione, F., Pappalardo, F., Bernaschi, M., Motta, S.: Optimization of HAART with genetic algorithms and agent-based models of HIV infection. Bioinformatics\u00a023, 3350\u20133355 (2007)","journal-title":"Bioinformatics"},{"key":"16_CR32","doi-asserted-by":"publisher","first-page":"1371","DOI":"10.1093\/bioinformatics\/btm044","volume":"23","author":"F. Castiglione","year":"2007","unstructured":"Castiglione, F., Duca, K., Jarrah, A., Laubenbacher, R., Hochberg, D., Thorley-Lawson, D.: Simulating Epstein-Barr virus infection with C-ImmSim. Bioinformatics\u00a023, 1371\u20131377 (2007)","journal-title":"Bioinformatics"},{"key":"16_CR33","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1186\/1755-8794-4-28","volume":"4","author":"T. Clancy","year":"2011","unstructured":"Clancy, T., Pedicini, M., Castiglione, F., Santoni, D., Nygaard, V., Lavelle, T.J., Benson, M., Hovig, E.: Immunological network signatures of cancer progression and survival. BMC Med. Genomics\u00a04, 28 (2011)","journal-title":"BMC Med. Genomics"},{"key":"16_CR34","doi-asserted-by":"crossref","unstructured":"Woelke, A.L., von Eichborn, J., Murgueitio, M.S., Worth, C.L., Castiglione, F., Preissner, R.: Development of immune-specific interaction potentials and their application in the multi-agent-system VaccImm. PLoS One 6, e23257 (2011)","DOI":"10.1371\/journal.pone.0023257"},{"key":"16_CR35","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1016\/j.biosystems.2005.10.004","volume":"84","author":"L. Mendoza","year":"2006","unstructured":"Mendoza, L.: A network model for the control of the differentiation process in Th cells. Biosystems\u00a084, 101\u2013114 (2006)","journal-title":"Biosystems"},{"key":"16_CR36","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1007\/s12064-010-0112-x","volume":"129","author":"L. Mendoza","year":"2010","unstructured":"Mendoza, L., Pardo, F.: A robust model to describe the differentiation of T-helper cells. Theory Biosci.\u00a0129, 283\u2013293 (2010)","journal-title":"Theory Biosci."},{"key":"16_CR37","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1016\/j.biosystems.2013.05.007","volume":"113","author":"P. Mart\u00ednez-Sosa","year":"2013","unstructured":"Mart\u00ednez-Sosa, P., Mendoza, L.: The regulatory network that controls the differentiation of T lymphocytes. Biosystems\u00a0113, 96\u2013103 (2013)","journal-title":"Biosystems"},{"key":"16_CR38","doi-asserted-by":"publisher","first-page":"1374","DOI":"10.1093\/bioinformatics\/btn135","volume":"24","author":"D. Santoni","year":"2008","unstructured":"Santoni, D., Pedicini, M., Castiglione, F.: Implementation of a regulatory gene network to simulate the TH1\/2 differentiation in an agent-based model of hypersensitivity reactions. Bioinformatics\u00a024, 1374\u20131380 (2008)","journal-title":"Bioinformatics"},{"key":"16_CR39","unstructured":"Janeway Ca Jr., T.P.W.M., et al.: Immunobiology: The Immune System in Health and Disease, 5th edn. Garland Science (2001)"},{"key":"16_CR40","doi-asserted-by":"crossref","unstructured":"Watanabe, S., Inoue, J.: Intracellular delivery of lipopolysaccharide induces effective Th1-immune responses independent of IL-12. PLoS One 8, e68671 (2013)","DOI":"10.1371\/journal.pone.0068671"},{"key":"16_CR41","doi-asserted-by":"publisher","first-page":"453","DOI":"10.2741\/2692","volume":"13","author":"F.O. Martinez","year":"2008","unstructured":"Martinez, F.O., Sica, A., Mantovani, A., Locati, M.: Macrophage activation and polarization. Front Biosci.\u00a013, 453\u2013461 (2008)","journal-title":"Front Biosci."},{"key":"16_CR42","doi-asserted-by":"publisher","first-page":"2506","DOI":"10.1002\/eji.1830241037","volume":"24","author":"D.D. Duncan","year":"1994","unstructured":"Duncan, D.D., Swain, S.L.: Role of antigen-presenting cells in the polarized development of helper T cell subsets: evidence for differential cytokine production by Th0 cells in response to antigen presentation by B cells and macrophages. Eur. J. Immunol.\u00a024, 2506\u20132514 (1994)","journal-title":"Eur. J. Immunol."},{"key":"16_CR43","doi-asserted-by":"publisher","first-page":"1091","DOI":"10.1084\/jem.176.4.1091","volume":"176","author":"R.A. Seder","year":"1992","unstructured":"Seder, R.A., Paul, W.E., Davis, M.M., de St. Groth, B.F.: The presence of interleukin 4 during in vitro priming determines the lymphokine-producing potential of CD4+ T cells from T cell receptor transgenic mice. J. Exp. Med.\u00a0176, 1091\u20131098 (1992)","journal-title":"J. Exp. Med."},{"key":"16_CR44","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1016\/j.immuni.2006.01.001","volume":"24","author":"M. Veldhoen","year":"2006","unstructured":"Veldhoen, M., Hocking, R.J., Atkins, C.J., Locksley, R.M., Stockinger, B.: TGFbeta in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-producing T cells. Immunity\u00a024, 179\u2013189 (2006)","journal-title":"Immunity"},{"key":"16_CR45","doi-asserted-by":"publisher","first-page":"1875","DOI":"10.1084\/jem.20030152","volume":"198","author":"W. Chen","year":"2003","unstructured":"Chen, W., Jin, W., Hardegen, N., Lei, K.-J., Li, L., Marinos, N., McGrady, G., Wahl, S.M.: Conversion of peripheral CD4+CD25- naive T cells to CD4+CD25+ regulatory T cells by TGF-beta induction of transcription factor Foxp3. J. Exp. Med.\u00a0198, 1875\u20131886 (2003)","journal-title":"J. Exp. Med."}],"container-title":["Lecture Notes in Computer Science","Advances in Bioinformatics and Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/978-3-319-12418-6_16","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,17]],"date-time":"2023-07-17T14:31:12Z","timestamp":1689604272000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/978-3-319-12418-6_16"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014]]},"ISBN":["9783319124179","9783319124186"],"references-count":45,"URL":"https:\/\/doi.org\/10.1007\/978-3-319-12418-6_16","relation":{},"ISSN":["0302-9743","1611-3349"],"issn-type":[{"value":"0302-9743","type":"print"},{"value":"1611-3349","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014]]}}}