Abstract
During an adaptive immune response, a population of naive lymphocytes becomes heterogeneous, containing a population of effector cells that clear the pathogen and then die during the contraction phase and a population of memory cells that are of a longer lineage. For CD8+ T cells, many theories have been proposed for the dynamics of this differentiation.
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References
Ahmed R, Bevan MJ, Reiner SL, Fearon DT (2009) The precursors of memory: models and controversies. Nat Rev Immunol 9(9):662–668
Badovinac VP, Haring JS, Harty JT (2007) Initial T cell receptor transgenic cell precursor frequency dictates critical aspects of the CD8+ T cell response to infection. Immunity 26(6):827–841
Buchholz VR, Flossdorf M, Hensel I, Kretschmer L, Weissbrich B, Gräf P, Verschoor A, Schiemann M, Höfer T, Busch DH (2013) Disparate individual fates compose robust CD8+ T cell immunity. Science 340(6132):630–635
Buchholz VR, Schumacher TNM, Busch DH (2016) T cell fate at the single-cell level. Ann Rev Immunol 34:65–92
Chang JT, Palanivel VR, Kinjyo I, Schambach F, Intlekofer AM, Banerjee A, Longworth SA, Vinup KE, Mrass P, Oliaro J, Killeen N, Orange JS, Russell SM, Weninger W, Reiner SL (2007) Asymmetric T lymphocyte division in the initiation of adaptive immune responses. Science 315(5819):1687–1691
Dowling MR, Kan A, Heinzel S, Zhou JHS, Marchingo JM, Wellard CJ, Markham JF, Hodgkin PD (2014) Stretched cell cycle model for proliferating lymphocytes. Proc Natl Acad Sci 111(17):6377–6382
Duffy KR, Wellard CJ, Markham JF, Zhou JHS, Holmberg R, Hawkins ED, Hasbold J, Dowling MR, Hodgkin PD (2012) Activation-induced B cell fates are selected by intracellular stochastic competition. Science 335(6066):338–341
Gerlach C, Rohr JC, Perié L, van Rooij N, van Heijst JWJ, Velds A, Urbanus J, Naik SH, Jacobs H, Beltman JB, de Boer RJ, Schumacher TNM (2013) Heterogeneous differentiation patterns of individual CD8+ T cells. Science 340(6132):635–639
Harris TE (1964) The theory of branching processes. The RAND Corporation
Hawkins ED, Turner ML, Dowling MR, van Gend C, Hodgkin PD (2007) A model of immune regulation as a consequence of randomized lymphocyte division and death times. Proc Natl Acad Sci 104(12):5032–5037
Hawkins ED, Markham JF, McGuinness LP, Hodgkin PD (2009) A single-cell pedigree analysis of alternative stochastic lymphocyte fates. Proc Natl Acad Sci 106(32):13457–13462
Heinzel S, Giang TB, Kan A, Marchingo JM, Lye BK, Corcoran LM, Hodgkin PD (2017) A Myc-dependent division timer complements a cell-death timer to regulate T cell and B cell responses. Nat Immunol 18:96–103
Jacob J, Baltimore D (1999) Modelling T-cell memory by genetic marking of memory T cells in vivo. Nature 399:593–597
King CG, Koehli S, Hausmann B, Schmaler M, Zehn D, Palmer E (2012) T cell affinity regulates asymmetric division, effector cell differentiation, and tissue pathology. Immunity 37(4):709–720
Kinjyo I, Qin J, Tan S-Y, Wellard CJ, Mrass P, Ritchie W, Doi A, Cavanagh LL, Tomura M, Sakaue-Sawano A, Kanagawa O, Miyawaki A, Hodgkin PD, Weninger W (2015) Real-time tracking of cell cycle progression during CD8+ effector and memory T-cell differentiation. Nat Commun 6:6301 EP
Lemaître F, Moreau HD, Vedele L, Bousso P (2013) Phenotypic CD8+ T cell diversification occurs before, during, and after the first T cell division. J Immunol 191(4):1578–1585
Marchingo JM, Kan A, Sutherland RM, Duffy KR, Wellard CJ, Belz GT, Lew AM, Dowling MR, Heinzel S, Hodgkin PD (2014) Antigen affinity, costimulation, and cytokine inputs sum linearly to amplify T cell expansion. Science 346(6213):1123–1127
Marchingo JM, Prevedello G, Kan A, Heinzel S, Hodgkin PD, Duffy KR (2016) T-cell stimuli independently sum to regulate an inherited clonal division fate. Nat Commun 7:13540
Opferman JT, Ober BT, Ashton-Rickardt PG (1999) Linear differentiation of cytotoxic effectors into memory T lymphocytes. Science 283(5408):1745–1748
Sakaue-Sawano A, Kurokawa H, Morimura T, Hanyu A, Hama H, Osawa H, Kashiwagi S, Fukami K, Miyata T, Miyoshi H, Imamura T, Ogawa M, Masai H, Miyawaki A (2008) Visualizing spatiotemporal dynamics of multicellular cell-cycle progression. Cell 132(3):487–498
Schlub TE, Badovinac VP, Sabea JT, Harty JT, Davenport MP (2010) Predicting CD62L expression during the CD8+ T cell response in vivo. Immunol Cell Biol 88(2):157–164
Smith JA, Martin L (1973) Do cells cycle? Proc Natl Acad Sci 70(4):1263–1267
Wherry EJ, Teichgräber V, Becker TC, Masopust D, Kaech SM, Antia R, von Andrian UH, Ahmed R (2003) Lineage relationship and protective immunity of memory CD8 T cell subsets. Nat Immunol 4:225–234
Acknowledgements
The work of A.M. and K.R.D. was supported by Science Foundation Ireland Grant 12IP1263. This work was supported by the National Health and Medical Research Council of Australia via Project Grant 1010654, Program Grant 1054925, and a fellowship to P.D.H. as well as an Australian Government National Health and Medical Research Council Independent Research Institutes Infrastructure Support Scheme Grant 361646.
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Miles, A.S., Hodgkin, P.D., Duffy, K.R. (2021). Inferring Differentiation Order in Adaptive Immune Responses from Population-Level Data. In: Molina-ParÃs, C., Lythe, G. (eds) Mathematical, Computational and Experimental T Cell Immunology. Springer, Cham. https://doi.org/10.1007/978-3-030-57204-4_9
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