Defining Memory CD8 T Cell

CD8 T cells comprising the memory pool display considerable heterogeneity, with individual cells differing in phenotype and function. This review will focus on our current understanding of heterogeneity within the antigen-specific memory CD8 T cell compartment and classifications of memory CD8 T cell subsets with defined and discrete functionalities. Recent data suggest that phenotype and/or function of numerically stable circulatory memory CD8 T cells are defined by the age of memory CD8 T cell (or time after initial antigen-encounter). In addition, history of antigen stimulations has a profound effect on memory CD8 T cell populations, suggesting that repeated infections (or vaccination) have the capacity to further shape the memory CD8 T cell pool. Finally, genetic background of hosts and history of exposure to diverse microorganisms likely contribute to the observed heterogeneity in the memory CD8 T cell compartment. Extending our tool box and exploring alternative mouse models (i.e., “dirty” and/or outbred mice) to encompass and better model diversity observed in humans will remain an important goal for the near future that will likely shed new light into the mechanisms that govern biology of memory CD8 T cells.

[1]  J. Harty,et al.  Repeated Antigen Exposure Extends the Durability of Influenza-Specific Lung-Resident Memory CD8+ T Cells and Heterosubtypic Immunity. , 2018, Cell reports.

[2]  Y. Kluger,et al.  KLRG1+ Effector CD8+ T Cells Lose KLRG1, Differentiate into All Memory T Cell Lineages, and Convey Enhanced Protective Immunity , 2018, Immunity.

[3]  S. Varga,et al.  The CD8 T Cell Response to Respiratory Virus Infections , 2018, Front. Immunol..

[4]  A. Folgori,et al.  Induction and Maintenance of CX3CR1-Intermediate Peripheral Memory CD8+ T Cells by Persistent Viruses and Vaccines , 2018, Cell reports.

[5]  Jason S. Mitchell,et al.  T Cells in Nonlymphoid Tissues Give Rise to Lymph‐Node‐Resident Memory T Cells , 2018, Immunity.

[6]  Jason S. Mitchell,et al.  Intravital mucosal imaging of CD8+ resident memory T cells shows tissue-autonomous recall responses that amplify secondary memory , 2018, Nature Immunology.

[7]  Scott N. Mueller,et al.  Local proliferation maintains a stable pool of tissue-resident memory T cells after antiviral recall responses , 2018, Nature Immunology.

[8]  G. Alexe,et al.  Origin and differentiation of human memory CD8 T cells after vaccination , 2017, Nature.

[9]  Koichi Araki,et al.  EFFECTOR CD8 T CELLS DEDIFFERENTIATE INTO LONG-LIVED MEMORY CELLS , 2017, Nature.

[10]  M. D. Martin,et al.  Revealing the Complexity in CD8 T Cell Responses to Infection in Inbred C57B/6 versus Outbred Swiss Mice , 2017, Front. Immunol..

[11]  Martin T. Ferris,et al.  Extensive Homeostatic T Cell Phenotypic Variation within the Collaborative Cross , 2017, Cell Reports.

[12]  J. Harty,et al.  Polymicrobial sepsis impairs bystander recruitment of effector cells to infected skin despite optimal sensing and alarming function of skin resident memory CD8 T cells , 2017, PLoS pathogens.

[13]  J. Utikal,et al.  Personalized RNA mutanome vaccines mobilize poly-specific therapeutic immunity against cancer , 2017, Nature.

[14]  A. Meryk,et al.  Increased IL-15 Production and Accumulation of Highly Differentiated CD8+ Effector/Memory T Cells in the Bone Marrow of Persons with Cytomegalovirus , 2017, Front. Immunol..

[15]  M. D. Martin,et al.  Time and Antigen-Stimulation History Influence Memory CD8 T Cell Bystander Responses , 2017, Front. Immunol..

[16]  R. Sékaly,et al.  Human memory CD8 T cell effector potential is epigenetically preserved during in vivo homeostasis , 2017, The Journal of experimental medicine.

[17]  John T. Chang,et al.  Epigenetic landscapes reveal transcription factors regulating CD8+ T cell differentiation , 2017, Nature Immunology.

[18]  K. Legge,et al.  Antigen Exposure History Defines CD8 T Cell Dynamics and Protection during Localized Pulmonary Infections , 2017, Front. Immunol..

[19]  J. Harty,et al.  Dynamics of influenza-induced lung-resident memory T cells underlie waning heterosubtypic immunity , 2017, Science Immunology.

[20]  U. V. von Andrian,et al.  The Chemokine Receptor CX3CR1 Defines Three Antigen-Experienced CD8 T Cell Subsets with Distinct Roles in Immune Surveillance and Homeostasis. , 2016, Immunity.

[21]  Scott N. Mueller,et al.  Liver-Resident Memory CD8+ T Cells Form a Front-Line Defense against Malaria Liver-Stage Infection. , 2016, Immunity.

[22]  L. Hunter,et al.  Aging promotes acquisition of naive-like CD8+ memory T cell traits and enhanced functionalities. , 2016, The Journal of clinical investigation.

[23]  Matheus C. Bürger,et al.  Sequential Infection with Common Pathogens Promotes Human-like Immune Gene Expression and Altered Vaccine Response. , 2016, Cell host & microbe.

[24]  W. Shi,et al.  Hobit and Blimp1 instruct a universal transcriptional program of tissue residency in lymphocytes , 2016, Science.

[25]  W. Haining,et al.  Normalizing the environment recapitulates adult human immune traits in laboratory mice , 2016, Nature.

[26]  P. Thomas,et al.  Balancing Immune Protection and Immune Pathology by CD8+ T-Cell Responses to Influenza Infection , 2016, Front. Immunol..

[27]  D. Pellicci,et al.  T-box Transcription Factors Combine with the Cytokines TGF-β and IL-15 to Control Tissue-Resident Memory T Cell Fate. , 2015, Immunity.

[28]  Corinne J. Smith,et al.  Murine CMV Infection Induces the Continuous Production of Mucosal Resident T Cells. , 2015, Cell reports.

[29]  A. Oxenius,et al.  The Salivary Gland Acts as a Sink for Tissue-Resident Memory CD8(+) T Cells, Facilitating Protection from Local Cytomegalovirus Infection. , 2015, Cell reports.

[30]  R. Sompallae,et al.  Phenotypic and Functional Alterations in Circulating Memory CD8 T Cells with Time after Primary Infection , 2015, PLoS pathogens.

[31]  M. Mann,et al.  Functional classification of memory CD8+ T cells by CX3CR1 expression , 2015, Nature Communications.

[32]  B. Igyártó,et al.  Quantifying Memory CD8 T Cells Reveals Regionalization of Immunosurveillance , 2015, Cell.

[33]  Michael Gale,et al.  Genetic Diversity in the Collaborative Cross Model Recapitulates Human West Nile Virus Disease Outcomes , 2015, mBio.

[34]  Nicholas Collins,et al.  Cutting Edge: CD69 Interference with Sphingosine-1-Phosphate Receptor Function Regulates Peripheral T Cell Retention , 2015, The Journal of Immunology.

[35]  Yufeng Shen,et al.  Spatial Map of Human T Cell Compartmentalization and Maintenance over Decades of Life , 2014, Cell.

[36]  Ji-Ying Song,et al.  Skin-resident memory CD8+ T cells trigger a state of tissue-wide pathogen alert , 2014, Science.

[37]  J. Schenkel,et al.  Resident memory CD8 T cells trigger protective innate and adaptive immune responses , 2014, Science.

[38]  V. Badovinac,et al.  The Longevity of Memory CD8 T Cell Responses after Repetitive Antigen Stimulations , 2014, The Journal of Immunology.

[39]  Tao Wu,et al.  Lung‐resident memory CD8 T cells (TRM) are indispensable for optimal cross‐protection against pulmonary virus infection , 2014, Journal of leukocyte biology.

[40]  D. Barber,et al.  Intravascular staining for discrimination of vascular and tissue leukocytes , 2014, Nature Protocols.

[41]  S. Kaech,et al.  Lung airway-surveilling CXCR3(hi) memory CD8(+) T cells are critical for protection against influenza A virus. , 2013, Immunity.

[42]  David L. Aylor,et al.  Using the emerging Collaborative Cross to probe the immune system , 2013, Genes and Immunity.

[43]  Scott N. Mueller,et al.  The developmental pathway for CD103+CD8+ tissue-resident memory T cells of skin , 2013, Nature Immunology.

[44]  S. Jameson,et al.  Transcriptional downregulation of S1pr1 is required for establishment of resident memory CD8+ T cells , 2013, Nature Immunology.

[45]  M. Bevan,et al.  Transforming growth factor-β signaling controls the formation and maintenance of gut-resident memory T cells by regulating migration and retention. , 2013, Immunity.

[46]  Mario Roederer,et al.  Protection Against Malaria by Intravenous Immunization with a Nonreplicating Sporozoite Vaccine , 2013, Science.

[47]  S. Jameson,et al.  Preexisting high frequencies of memory CD8+ T cells favor rapid memory differentiation and preservation of proliferative potential upon boosting. , 2013, Immunity.

[48]  S. Jameson,et al.  Effector-like CD8⁺ T cells in the memory population mediate potent protective immunity. , 2013, Immunity.

[49]  J. Schenkel,et al.  Sensing and alarm function of resident memory CD8+ T cells , 2013, Nature Immunology.

[50]  M. Sykes,et al.  Distribution and compartmentalization of human circulating and tissue-resident memory T cell subsets. , 2013, Immunity.

[51]  Scott N. Mueller,et al.  Long-lived epithelial immunity by tissue-resident memory T (TRM) cells in the absence of persisting local antigen presentation , 2012, Proceedings of the National Academy of Sciences.

[52]  J. Harty,et al.  Division-linked generation of death-intermediates regulates the numerical stability of memory CD8 T cells , 2012, Proceedings of the National Academy of Sciences.

[53]  R. Clark,et al.  Skin infection generates non-migratory memory CD8+ TRM cells providing global skin immunity , 2012, Nature.

[54]  J. Harty,et al.  Population Dynamics of Naive and Memory CD8 T Cell Responses after Antigen Stimulations In Vivo , 2012, The Journal of Immunology.

[55]  Leonard McMillan,et al.  High-Resolution Genetic Mapping Using the Mouse Diversity Outbred Population , 2012, Genetics.

[56]  G. Churchill,et al.  Ten Years of the Collaborative Cross , 2012, Genetics.

[57]  G. V. D. van der Windt,et al.  Mitochondrial respiratory capacity is a critical regulator of CD8+ T cell memory development. , 2012, Immunity.

[58]  E. Yang,et al.  The transcriptional regulators Id2 and Id3 control the formation of distinct memory CD8+ T cell subsets , 2011, Nature Immunology.

[59]  S. Kaech,et al.  An interleukin-21-interleukin-10-STAT3 pathway is critical for functional maturation of memory CD8+ T cells. , 2011, Immunity.

[60]  E. R. James,et al.  Live Attenuated Malaria Vaccine Designed to Protect Through Hepatic CD8+ T Cell Immunity , 2011, Science.

[61]  F. Marincola,et al.  Repression of the DNA-binding inhibitor Id3 by Blimp-1 limits CD8+ T cell memory formation , 2011, Nature Immunology.

[62]  J. Sprent,et al.  Normal T cell homeostasis: the conversion of naive cells into memory-phenotype cells , 2011, Nature Immunology.

[63]  J. Harty,et al.  Protective capacity of memory CD8+ T cells is dictated by antigen exposure history and nature of the infection. , 2011, Immunity.

[64]  Thomas C. Wirth,et al.  Secondary CD8+ T‐cell responses are controlled by systemic inflammation , 2011, European journal of immunology.

[65]  R. Ahmed,et al.  Insights into human CD8+ T‐cell memory using the yellow fever and smallpox vaccines , 2011, Immunology and cell biology.

[66]  E. Wherry,et al.  Cutting Edge: The Transcription Factor Eomesodermin Enables CD8+ T Cells To Compete for the Memory Cell Niche , 2010, The Journal of Immunology.

[67]  J. Harty,et al.  Differentiation and persistence of memory CD8(+) T cells depend on T cell factor 1. , 2010, Immunity.

[68]  J. Harty,et al.  Repetitive antigen stimulation induces stepwise transcriptome diversification but preserves a core signature of memory CD8(+) T cell differentiation. , 2010, Immunity.

[69]  J. Harty,et al.  Tracking the Total CD8 T Cell Response to Infection Reveals Substantial Discordance in Magnitude and Kinetics between Inbred and Outbred Hosts1 , 2009, The Journal of Immunology.

[70]  E. Meffre,et al.  Transcriptional repressor Blimp-1 promotes CD8(+) T cell terminal differentiation and represses the acquisition of central memory T cell properties. , 2009, Immunity.

[71]  D. Masopust Developing an HIV cytotoxic T‐lymphocyte vaccine: issues of CD8 T‐cell quantity, quality and location , 2009, Journal of internal medicine.

[72]  Lyric C. Bartholomay,et al.  Memory CD8 T cell responses exceeding a large but definable threshold provide long-term immunity to malaria , 2008, Proceedings of the National Academy of Sciences.

[73]  D. Dolfi,et al.  Late Signals from CD27 Prevent Fas-Dependent Apoptosis of Primary CD8+ T Cells1 , 2008, The Journal of Immunology.

[74]  John T. Harty,et al.  Shaping and reshaping CD8+ T-cell memory , 2008, Nature Reviews Immunology.

[75]  Nikhil S. Joshi,et al.  Inflammation directs memory precursor and short-lived effector CD8(+) T cell fates via the graded expression of T-bet transcription factor. , 2007, Immunity.

[76]  S. Kaech,et al.  Expression of IL-7 receptor α is necessary but not sufficient for the formation of memory CD8 T cells during viral infection , 2007, Proceedings of the National Academy of Sciences.

[77]  Alan D. Roberts,et al.  Activation phenotype, rather than central– or effector–memory phenotype, predicts the recall efficacy of memory CD8+ T cells , 2007, The Journal of experimental medicine.

[78]  A. Goldrath,et al.  Transcriptional regulator Id2 mediates CD8+ T cell immunity , 2006, Nature Immunology.

[79]  Sang-Jun Ha,et al.  Stimulation history dictates memory CD8 T cell phenotype: implications for prime-boost vaccination. , 2006, Journal of immunology.

[80]  Christian Stemberger,et al.  Unidirectional development of CD8+ central memory T cells into protective Listeria‐specific effector memory T cells , 2006, European journal of immunology.

[81]  J. Harty,et al.  Programming, demarcating, and manipulating CD8+ T‐cell memory , 2006, Immunological reviews.

[82]  J. Harty,et al.  Secondary memory CD8+ T cells are more protective but slower to acquire a central–memory phenotype , 2006, The Journal of experimental medicine.

[83]  E. Wherry,et al.  Effector and memory CD8+ T cell fate coupled by T-bet and eomesodermin , 2005, Nature Immunology.

[84]  Marie-Pierre Hardy,et al.  IL-7 Receptor Expression Levels Do Not Identify CD8+ Memory T Lymphocyte Precursors following Peptide Immunization1 , 2005, The Journal of Immunology.

[85]  Martin F. Bachmann,et al.  Functional Properties and Lineage Relationship of CD8+ T Cell Subsets Identified by Expression of IL-7 Receptor α and CD62L1 , 2005, The Journal of Immunology.

[86]  Alan D. Roberts,et al.  Differential contributions of central and effector memory T cells to recall responses , 2005, The Journal of experimental medicine.

[87]  J. Harty,et al.  Accelerated CD8+ T-cell memory and prime-boost response after dendritic-cell vaccination , 2005, Nature Medicine.

[88]  E. Pamer Immune responses to Listeria monocytogenes , 2004, Nature Reviews Immunology.

[89]  T. Tokuhisa,et al.  Bcl6 Acts as an Amplifier for the Generation and Proliferative Capacity of Central Memory CD8+ T Cells1 , 2004, The Journal of Immunology.

[90]  L. Lefrançois,et al.  Dynamics of blood-borne CD8 memory T cell migration in vivo. , 2004, Immunity.

[91]  R. Ward,et al.  Activated Primary and Memory CD8 T Cells Migrate to Nonlymphoid Tissues Regardless of Site of Activation or Tissue of Origin1 , 2004, The Journal of Immunology.

[92]  P. Doherty,et al.  The Collagen Binding α1β1 Integrin VLA-1 Regulates CD8 T Cell-Mediated Immune Protection against Heterologous Influenza Infection , 2004 .

[93]  E. Wherry,et al.  Selective expression of the interleukin 7 receptor identifies effector CD8 T cells that give rise to long-lived memory cells , 2003, Nature Immunology.

[94]  E. Wherry,et al.  Cutting Edge: Rapid In Vivo Killing by Memory CD8 T Cells1 , 2003, The Journal of Immunology.

[95]  Rustom Antia,et al.  Lineage relationship and protective immunity of memory CD8 T cell subsets , 2003, Nature Immunology.

[96]  Susan M. Kaech,et al.  Molecular and Functional Profiling of Memory CD8 T Cell Differentiation , 2002, Cell.

[97]  J. Harty,et al.  Programmed contraction of CD8+ T cells after infection , 2002, Nature Immunology.

[98]  J. Whitton,et al.  Functional avidity maturation of CD8+ T cells without selection of higher affinity TCR , 2001, Nature Immunology.

[99]  Dirk Homann,et al.  Differential regulation of antiviral T-cell immunity results in stable CD8+ but declining CD4+ T-cell memory , 2001, Nature Medicine.

[100]  L. Lefrançois,et al.  Preferential Localization of Effector Memory Cells in Nonlymphoid Tissue , 2001, Science.

[101]  S. Jameson,et al.  Interleukin-7 mediates the homeostasis of naïve and memory CD8 T cells in vivo , 2000, Nature Immunology.

[102]  Henrique Veiga-Fernandes,et al.  Response of naïve and memory CD8+ T cells to antigen stimulation in vivo , 2000, Nature Immunology.

[103]  J. Whitton,et al.  Activated and Memory CD8+ T Cells Can Be Distinguished by Their Cytokine Profiles and Phenotypic Markers1 , 2000, The Journal of Immunology.

[104]  M. Weekes,et al.  Large clonal expansions of human virus‐specific memory cytotoxic T lymphocytes within the CD57+ CD28– CD8+ T‐cell population , 1999, Immunology.

[105]  F. Sallusto,et al.  Two subsets of memory T lymphocytes with distinct homing potentials and effector functions , 1999, Nature.

[106]  M. Rep,et al.  Phenotypic and Functional Separation of Memory and Effector Human CD8+ T Cells , 1997, The Journal of experimental medicine.

[107]  A. McMichael,et al.  Rapid Effector Function in CD8+ Memory T Cells , 1997, The Journal of experimental medicine.

[108]  S. Jameson,et al.  Innate memory T cells. , 2015, Advances in immunology.

[109]  Hao Shen,et al.  Quick to remember, slow to forget: rapid recall responses of memory CD8+ T cells , 2010, Cell Research.

[110]  P. Doherty,et al.  The collagen binding alpha1beta1 integrin VLA-1 regulates CD8 T cell-mediated immune protection against heterologous influenza infection. , 2004, Immunity.

[111]  B. Rocha,et al.  High expression of active CDK6 in the cytoplasm of CD8 memory cells favors rapid division , 2004, Nature Immunology.

[112]  The Complex Trait Consortium The Collaborative Cross, a community resource for the genetic analysis of complex traits , 2004 .

[113]  J. Harty,et al.  Memory lanes , 2003, Nature Immunology.

[114]  of Infection , 2022 .