The smallest unit: Effector and memory CD8+ T cell differentiation on the single cell level

Frontiers in Immunology

Volumn 4, Issue FRB, 2013, Pages

  Buchholz, Veit R ^a   Gräf, Patricia ^a   Busch, Dirk H ^a,b  

^a TECHNICAL UNIVERSITY OF MUNICH   (Germany)

^b DZIF National Centre for Infection Research   (Germany)

Author keywords

Memory ontogeny; Single cell fate mapping; Single cell resolution; Subset diversification; T memory stem cell

Indexed keywords

ABC TRANSPORTER; BETA CATENIN; EPITOPE; GAMMA INTERFERON; INTERLEUKIN 15; INTERLEUKIN 15 RECEPTOR ALPHA; INTERLEUKIN 2; INTERLEUKIN 7; INTERLEUKIN 7 RECEPTOR; L SELECTIN; LYMPHOID ENHANCER FACTOR 1; SMAD PROTEIN; STAT3 PROTEIN; T LYMPHOCYTE RECEPTOR; TRANSCRIPTION FACTOR 7; TRANSCRIPTION FACTOR FOXO; TUMOR NECROSIS FACTOR ALPHA; WNT PROTEIN;

CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; CELL CULTURE MONITORING; CELL DIFFERENTIATION; CELL RENEWAL; DENDRITIC CELL; FLOW CYTOMETRY; FLUORESCENCE MICROSCOPY; HELPER CELL; HEMATOPOIETIC STEM CELL; HUMAN; ISOTOPE LABELING; LYMPHOCYTE SUBPOPULATION; MAJOR HISTOCOMPATIBILITY COMPLEX; MASS SPECTROMETRY; MEMORY T LYMPHOCYTE; MULTIPOTENT STEM CELL; PHENOTYPE; PROTEIN EXPRESSION; REVIEW; SINGLE CELL ANALYSIS; T LYMPHOCYTE ACTIVATION; TIME OF FLIGHT MASS SPECTROMETRY; TOTIPOTENT STEM CELL;

EID: 84883720814     PISSN: None     EISSN: 16643224     Source Type: Journal    
DOI: 10.3389/fimmu.2013.00031     Document Type: Review

References (109)

1. Altman, J. D., Moss, P. A., Goulder, P. J., Barouch, D. H., McHeyzer-Williams, M. G., Bell, J. I., et al. (1996). Phenotypic analysis of antigen-specific T lymphocytes. Science 274, 94-96.
2. Appay, V., Douek, D. C., and Price, D. A. (2008). CD8+ T cell efficacy in vaccination and disease. Nat. Med. 14, 623-628.
3. Arstila, T. P., Casrouge, A., Baron, V., Even, J., Kanellopoulos, J., and Kourilsky, P. (1999). A direct estimate of the human alphabeta T cell receptor diversity. Science 286, 958-961.
4. Banerjee, A., Gordon, S. M., Intlekofer, A. M., Paley, M. A., Mooney, E. C., Lindsten, T., et al. (2010). Cutting edge: the transcription factor eomesodermin enables CD8+ T cells to compete for the memory cell niche. J. Immunol. 185, 4988-4992.
5. Bannard, O., Kraman, M., and Fearon, D. T. (2009). Secondary replicative function of CD8+ T cells that had developed an effector phenotype. Science 323, 505-509.
6. Bendall, S. C., Simonds, E. F., Qiu, P., Amir, E.-A. D., Krutzik, P. O., Finck, R., et al. (2011). Single-cell mass cytometry of differential immune and drug responses across a human hematopoietic continuum. Science 332, 687-696.
7. Betts, M. R., Nason, M. C., West, S. M., De Rosa, S. C., Migueles, S. A., Abraham, J., et al. (2006). HIV nonprogressors preferentially maintain highly functional HIV-specific CD8+ T cells. Blood 107, 4781-4789.
8. Betz, U. A., and Müller, W. (1998). Regulated expression of gp130 and IL-6 receptor alpha chain in T cell maturation and activation. Int. Immunol. 10, 1175-1184.
9. Beuneu, H., Lemaître, F., Deguine, J., Moreau, H. D., Bouvier, I., Garcia, Z., et al. (2010). Visualizing the functional diversification of CD8+ T cell responses in lymph nodes. Immunity 33, 412-423.
10. Buchholz, V. R., Gräf, P., and Busch, D. H. (2012). The origin of diversity: studying the evolution of multi-faceted CD8+ T cell responses. Cell. Mol. Life Sci. 69, 1585-1595.
11. Busch, D. H., Pilip, I. M., Vijh, S., and Pamer, E. G. (1998). Coordinate regulation of complex T cell populations responding to bacterial infection. Immunity 8, 353-362.
12. Casrouge, A., Beaudoing, E., Dalle, S., Pannetier, C., Kanellopoulos, J., and Kourilsky, P. (2000). Size estimate of the alpha beta TCR repertoire of naive mouse splenocytes. J. Immunol. 164, 5782-5787.
13. Castellino, F., and Germain, R. N. (2007). Chemokine-guided CD4+ T cell help enhances generation of IL-6RalphahighIL-7Ralpha high prememory CD8+ T cells. J. Immunol. 178, 778-787.
14. Celli, S., Garcia, Z., and Bousso, P. (2005). CD4 T cells integrate signals delivered during successive DC encounters in vivo. J. Exp. Med. 202, 1271-1278.
15. Chang, J. T., Ciocca, M. L., Kinjyo, I., Palanivel, V. R., McClurkin, C. E., Dejong, C. S., et al. (2011). Asymmetric proteasome segregation as a mechanism for unequal partitioning of the transcription factor T-bet during T lymphocyte division. Immunity 34, 492-504.
16. Chang, J. T., Palanivel, V. R., Kinjyo, I., Schambach, F., Intlekofer, A. M., Banerjee, A., et al. (2007). Asymmetric T lymphocyte division in the initiation of adaptive immune responses. Science 315, 1687-1691.
17. Chaudhary, P. M., and Roninson, I. B. (1991). Expression and activity of P-glycoprotein, a multidrug efflux pump, in human hematopoietic stem cells. Cell 66, 85-94.
18. Cieri, N., Camisa, B., Cocchiarella, F., Forcato, M., Oliveira, G., Provasi, E., et al. (2013). IL-7 and IL-15 instruct the generation of human memory stem T cells from naive precursors. Blood 121, 573-584.
19. Ciocca, M. L., Barnett, B. E., Burkhardt, J. K., Chang, J. T., and Reiner, S. L. (2012). Cutting edge: asymmetric memory T cell division in response to rechallenge. J. Immunol. 188, 4145-4148.
20. Creamer, B., Shorter, R. G., and Bamforth, J. (1961). The turnover and shedding of epithelial cells. I. The turnover in the gastro-intestinal tract. Gut 2, 110-118.
21. 3 pathway is critical for functional maturation of memory CD8+ T cells. Immunity 35, 792-805.
22. Darrah, P. A., Patel, D. T., De Luca, P. M., Lindsay, R. W. B., Davey, D. F., Flynn, B. J., et al. (2007). Multifunctional TH1 cells define a correlate of vaccine-mediated protection against Leishmania major. Nat. Med. 13, 843-850.
23. Doering, T. A., Crawford, A., Angelosanto, J. M., Paley, M. A., Ziegler, C. G., and Wherry, E. J. (2012). Network analysis reveals centrally connected genes and pathways involved in CD8(+) T cell exhaustion versus memory. Immunity 37, 1130-1144.
24. Dusseaux, M., Martin, E., Serriari, N., Péguillet, I., Premel, V., Louis, D., et al. (2011). Human MAIT cells are xenobiotic-resistant, tissue-targeted, CD161hi IL-17-secreting T cells. Blood 117, 1250-1259.
25. Dutton, R. W., Bradley, L. M., and Swain, S. L. (1998). T cell memory. Annu. Rev. Immunol. 16, 201-223.
26. Eilken, H. M., Nishikawa, S.-I., and Schroeder, T. (2009). Continuous single-cell imaging of blood generation from haemogenic endothelium. Nature 457, 896-900.
27. Feau, S., Arens, R., Togher, S., and Schoenberger, S. P. (2011). Autocrine IL-2 is required for secondary population expansion of CD8(+) memory T cells. Nat. Immunol. 12, 908-913.
28. Fleming, H. E., Janzen, V., Celso Lo, C., Guo, J., Leahy, K. M., Kronenberg, H. M., et al. (2008). Wnt signaling in the niche enforces hematopoietic stem cell quiescence and is necessary to preserve self-renewal in vivo. Cell Stem Cell 2, 274-283.
29. Fröhlich, A., Kisielow, J., Schmitz, I., Freigang, S., Shamshiev, A. T., Weber, J., et al. (2009). IL-21R on T cells is critical for sustained functionality and control of chronic viral infection. Science 324, 1576-1580.
30. Galli, M., Muñoz, J., Portegijs, V., Boxem, M., Grill, S. W., Heck, A. J. R., et al. (2011). aPKC phosphorylates NuMA-related LIN-5 to position the mitotic spindle during asymmetric division. Nat. Cell Biol. 13, 1132-1138.
31. Gattinoni, L., Klebanoff, C. A., Palmer, D. C., Wrzesinski, C., Kerstann, K., Yu, Z., et al. (2005). Acquisition of full effector function in vitro paradoxically impairs the in vivo antitumor efficacy of adoptively transferred CD8+ T cells. J. Clin. Invest. 115, 1616-1626.
32. Gattinoni, L., Klebanoff, C. A., and Restifo, N. P. (2012). Paths to stemness: building the ultimate antitumour T cell. Nat. Rev. Cancer 12, 671-684.
33. Gattinoni, L., Lugli, E., Ji, Y., Pos, Z., Paulos, C. M., Quigley, M. F., et al. (2011). A human memory T cell subset with stem cell-like properties. Nat. Med. 17, 1290-1297.
34. Gattinoni, L., Zhong, X.-S., Palmer, D. C., Ji, Y., Hinrichs, C. S., Yu, Z., et al. (2009). Wnt signaling arrests effector T cell differentiation and generates CD8+ memory stem cells. Nat. Med. 15, 808-813.
35. Gerlach, C., van Heijst, J. W. J., Swart, E., Sie, D., Armstrong, N., Kerkhoven, R. M., et al. (2010). One naive T cell, multiple fates in CD8+ T cell differentiation. J. Exp. Med. 207, 1235-1246.
36. Gett, A. V., Sallusto, F., Lanzavecchia, A., and Geginat, J. (2003). T cell fitness determined by signal strength. Nat. Immunol. 4, 355-360.
37. Hale, J. S., Boursalian, T. E., Turk, G. L., and Fink, P. J. (2006). Thymic output in aged mice. Proc. Natl. Acad. Sci. U.S.A. 103, 8447-8452.
38. 3K/AKT signaling on effector and memory CD8 T-cell survival. Proc. Natl. Acad. Sci. U.S.A. 107, 16601-16606.
39. Harari, A., Petitpierre, S., Vallelian, F., and Pantaleo, G. (2004). Skewed representation of functionally distinct populations of virus-specific CD4 T cells in HIV-1-infected subjects with progressive disease: changes after antiretroviral therapy. Blood 103, 966-972.
40. Havenith, S. H. C., Yong, S. L., Henson, S. M., Piet, B., Idu, M. M., Koch, S. D., et al. (2012). Analysis of stem-cell-like properties of human CD161++IL-18Rα+ memory CD8+ T cells. Int. Immunol. 24, 625-636.
41. Henrickson, S. E., Mempel, T. R., Mazo, I. B., Liu, B., Artyomov, M. N., Zheng, H., et al. (2008). T cell sensing of antigen dose governs interactive behavior with dendritic cells and sets a threshold for T cell activation. Nat. Immunol. 9, 282-291.
42. Henrickson, S. E., and von Andrian, U. H. (2007). Single-cell dynamics of T-cell priming. Curr. Opin. Immunol. 19, 249-258.
43. Holmes, S., He, M., Xu, T., and Lee, P. P. (2005). Memory T cells have gene expression patterns intermediate between naive and effector. Proc. Natl. Acad. Sci. U.S.A. 102, 5519-5523.
44. Huster, K. M., Busch, V., Schiemann, M., Linkemann, K., Kerksiek, K. M., Wagner, H., et al. (2004). Selective expression of IL-7 receptor on memory T cells identifies early CD40L-dependent generation of distinct CD8+ memory T cell subsets. Proc. Natl. Acad. Sci. U.S.A. 101, 5610-5615.
45. Intlekofer, A. M., Takemoto, N., Wherry, E. J., Longworth, S. A., Northrup, J. T., Palanivel, V. R., et al. (2005). Effector and memory CD8+ T cell fate coupled by T-bet and eomesodermin. Nat. Immunol. 6, 1236-1244.
46. Jacob, J., and Baltimore, D. (1999). Modelling T-cell memory by genetic marking of memory T cells in vivo. Nature 399, 593-597.
47. Jameson, S. C. (2002). Maintaining the norm: T-cell homeostasis. Nat. Rev. Immunol. 2, 547-556.
48. Jeannet, G., Boudousquié, C., Gardiol, N., Kang, J., Huelsken, J., and Held, W. (2010). Essential role of the Wnt pathway effector Tcf-1 for the establishment of functional CD8 T cell memory. Proc. Natl. Acad. Sci. U.S.A. 107, 9777-9782.
49. Ji, Y., Pos, Z., Rao, M., Klebanoff, C. A., Yu, Z., Sukumar, M., et al. (2011). Repression of the DNA-binding inhibitor Id3 by Blimp-1 limits the formation of memory CD8+ T cells. Nat. Immunol. 12, 1230-1237.
50. Jiang, Q., Li, W. Q., Aiello, F. B., Mazzucchelli, R., Asefa, B., Khaled, A. R., et al. (2005). Cell biology of IL-7, a key lymphotrophin. Cytokine Growth Factor Rev. 16, 513-533.
51. Joshi, N. S., Cui, W., Chandele, A., Lee, H. K., Urso, D. R., Hagman, J., et al. (2007). Inflammation directs memory precursor and short-lived effector CD8+ T cell fates via the graded expression of T-bet transcription factor. Immunity 27, 281-295.
52. Joshi, N. S., and Kaech, S. M. (2008). Effector CD8 T cell development: a balancing act between memory cell potential and terminal differentiation. J. Immunol. 180, 1309-1315.
53. Kaech, S. M., Tan, J. T., Wherry, E. J., Konieczny, B. T., Surh, C. D., and Ahmed, R. (2003). Selective expression of the interleukin 7 receptor identifies effector CD8 T cells that give rise to long-lived memory cells. Nat. Immunol. 4, 1191-1198.
54. Kim, E. H., Sullivan, J. A., Plisch, E. H., Tejera, M. M., Jatzek, A., Choi, K. Y., et al. (2012). Signal integration by Akt regulates CD8 T cell effector and memory differentiation. J. Immunol. 188, 4305-4314.
55. King, C. G., Koehli, S., Hausmann, B., Schmaler, M., Zehn, D., and Palmer, E. (2012). T cell affinity regulates asymmetric division, effector cell differentiation, and tissue pathology. Immunity 37, 709-720.
56. Leonard, W. J., and Spolski, R. (2005). Interleukin-21: a modulator of lymphoid proliferation, apoptosis and differentiation. Nat. Rev. Immunol. 5, 688-698.
57. Li, Y., Bleakley, M., and Yee, C. (2005). IL-21 influences the frequency, phenotype, and affinity of the antigen-specific CD8 T cell response. J. Immunol. 175, 2261-2269.
58. Luckey, C. J., Bhattacharya, D., Goldrath, A. W., Weissman, I. L., Benoist, C., and Mathis, D. (2006). Memory T and memory B cells share a transcriptional program of self-renewal with long-term hematopoietic stem cells. Proc. Natl. Acad. Sci. U.S.A. 103, 3304-3309.
59. Lugli, E., Gattinoni, L., Roberto, A., Mavilio, D., Price, D. A., Restifo, N. P., et al. (2012). Identification, isolation and in vitro expansion of human and nonhuman primate T stem cell memory cells. Nat. Protoc. 8, 33-42.
60. Masopust, D., Vezys, V., Marzo, A. L., and Lefrançois, L. (2001). Preferential localization of effector memory cells in nonlymphoid tissue. Science 291, 2413-2417.
61. Mazzucchelli, R., and Durum, S. K. (2007). Interleukin-7 receptor expression: intelligent design. Nat. Rev. Immunol. 7, 144-154.
62. Mempel, T. R., Henrickson, S. E., and Andrian von, U. H. (2004). T-cell priming by dendritic cells in lymph nodes occurs in three distinct phases. Nature 427, 154-159.
63. Mizutani, T., Masuda, M., Nakai, E., Furumiya, K., Togawa, H., Nakamura, Y., et al. (2008). Genuine functions of P-glycoprotein (ABCB1). Curr. Drug Metab. 9, 167-174.
64. Moreau, H. D., Lemaître, F., Terriac, E., Azar, G., Piel, M., Lennon-Dumenil, A.-M., et al. (2012). Dynamic in situ cytometry uncovers T cell receptor signaling during immunological synapses and kinapses in vivo. Immunity 37, 351-363.
65. Morrison, S. J., and Spradling, A. C. (2008). Stem cells and niches: mechanisms that promote stem cell maintenance throughout life. Cell 132, 598-611.
66. Muralidharan, S., Hanley, P. J., Liu, E., Chakraborty, R., Bollard, C., Shpall, E., et al. (2011). Activation of Wnt signaling arrests effector differentiation in human peripheral and cord blood-derived T lymphocytes. J. Immunol. 187, 5221-5232.
67. Murali-Krishna, K., Lau, L. L., Sambhara, S., Lemonnier, F., Altman, J., and Ahmed, R. (1999). Persistence of memory CD8 T cells in MHC class I-deficient mice. Science 286, 1377-1381.
68. Newell, E. W., Sigal, N., Bendall, S. C., Nolan, G. P., and Davis, M. M. (2012). Cytometry by time-of-flight shows combinatorial cytokine expression and virus-specific cell niches within a continuum of CD8+ T cell phenotypes. Immunity 36, 142-152.
69. Osawa, M., Hanada, K., Hamada, H., and Nakauchi, H. (1996). Long-term lymphohematopoietic reconstitution by a single CD34-low/negative hematopoietic stem cell. Science 273, 242-245.
70. Paley, M. A., Kroy, D. C., Odorizzi, P. M., Johnnidis, J. B., Dolfi, D. V., Barnett, B. E., et al. (2012). Progenitor and terminal subsets of CD8+ T cells cooperate to contain chronic viral infection. Science 338, 1220-1225.
71. Pearce, E. L., Mullen, A. C., Martins, G. A., Krawczyk, C. M., Hutchins, A. S., Zediak, V. P., et al. (2003). Control of effector CD8+ T cell function by the transcription factor Eomesodermin. Science 302, 1041-1043.
72. Perfetto, S. P., Chattopadhyay, P. K., and Roederer, M. (2004). Seventeen-colour flow cytometry: unravelling the immune system. Nat. Rev. Immunol. 4, 648-655.
73. Rao, R. R., Li, Q., Gubbels Bupp, M. R., and Shrikant, P. A. (2012). Transcription factor Foxo1 represses T-bet-mediated effector functions and promotes memory CD8(+) T cell differentiation. Immunity 36, 374-387.
74. Rao, R. R., Li, Q., Odunsi, K., and Shrikant, P. A. (2010). The mTOR kinase determines effector versus memory CD8+ T cell fate by regulating the expression of transcription factors T-bet and Eomesodermin. Immunity 32, 67-78.
75. Sallusto, F., Lanzavecchia, A., Araki, K., and Ahmed, R. (2010). From vaccines to memory and back. Immunity 33, 451-463.
76. Sallusto, F., Lenig, D., Förster, R., Lipp, M., and Lanzavecchia, A. (1999). Two subsets of memory T lymphocytes with distinct homing potentials and effector functions. Nature 401, 708-712.
77. Sarkar, S., Kalia, V., Haining, W. N., Konieczny, B. T., Subramaniam, S., and Ahmed, R. (2008). Functional and genomic profiling of effector CD8 T cell subsets with distinct memory fates. J. Exp. Med. 205, 625-640.
78. Schepers, K., Swart, E., van Heijst, J. W., Gerlach, C., Castrucci, M., Sie, D., et al. (2008). Dissecting T cell lineage relationships by cellular barcoding. J. Exp. Med. 205, 2309-2318.
79. Schluns, K. S., and Lefrançois, L. (2003). Cytokine control of memory T-cell development and survival. Nat. Rev. Immunol. 3, 269-279.
80. Schluns, K. S., Williams, K., Ma, A., Zheng, X. X., and Lefrançois, L. (2002). Cutting edge: requirement for IL-15 in the generation of primary and memory antigen-specific CD8 T cells. J. Immunol. 168, 4827-4831.
81. Schumacher, T. N. M., Gerlach, C., and van Heijst, J. W. J. (2010). Mapping the life histories of T cells. Nat. Rev. Immunol. 10, 621-631.
82. Seder, R. A., Darrah, P. A., and Roederer, M. (2008). T-cell quality in memory and protection: implications for vaccine design. Nat. Rev. Immunol. 8, 247-258.
83. 3 transcription factor signaling in the development and maintenance of human T cell memory. Immunity 35, 806-818.
84. Simons, B. D., and Clevers, H. (2011). Strategies for homeostatic stem cell self-renewal in adult tissues. Cell 145, 851-862.
85. Spangrude, G. J., Heimfeld, S., and Weissman, I. L. (1988). Purification and characterization of mouse hematopoietic stem cells. Science 241, 58-62.
86. Staal, F. J. T., Luis, T. C., and Tiemessen, M. M. (2008). WNT signalling in the immune system: WNT is spreading its wings. Nat. Rev. Immunol. 8, 581-593.
87. Steinmann, G. G. (1986). Changes in the human thymus during aging. Curr. Top. Pathol. 75, 43-88.
88. Stemberger, C., Huster, K. M., Koffler, M., Anderl, F., Schiemann, M., Wagner, H., et al. (2007). A single naive CD8+ T cell precursor can develop into diverse effector and memory subsets. Immunity 27, 985-997.
89. Stemberger, C., Neuenhahn, M., Gebhardt, F. E., Schiemann, M., Buchholz, V. R., and Busch, D. H. (2009). Stem cell-like plasticity of naïve and distinct memory CD8+ T cell subsets. Semin. Immunol. 21, 62-68.
90. Stoll, S., Delon, J., Brotz, T. M., and Germain, R. N. (2002). Dynamic imaging of T cell-dendritic cell interactions in lymph nodes. Science 296, 1873-1876.
91. Sun, T. T., and Green, H. (1976). Differentiation of the epidermal keratinocyte in cell culture: formation of the cornified envelope. Cell 9, 511-521.
92. Szabo, S. J., Kim, S. T., Costa, G. L., Zhang, X., Fathman, C. G., and Glimcher, L. H. (2000). A novel transcription factor, T-bet, directs Th1 lineage commitment. Cell 100, 655-669.
93. Thaventhiran, J. E. D., Hoffmann, A., Magiera, L., la Roche de, M., Lingel, H., Brunner-Weinzierl, M., et al. (2012). Activation of the Hippo pathway by CTLA-4 regulates the expression of Blimp-1 in the CD8+ T cell. Proc. Natl. Acad. Sci. U.S.A. 109, E2223-E2229.
94. Turtle, C. J., Delrow, J., Joslyn, R. C., Swanson, H. M., Basom, R., Tabellini, L., et al. (2011). Innate signals overcome acquired TCR signaling pathway regulation and govern the fate of human CD161hi CD8{alpha}+ semi-invariant T cells. Blood 118, 2752-2762.
95. Turtle, C. J., Swanson, H. M., Fujii, N., Estey, E. H., and Riddell, S. R. (2009). A distinct subset of self-renewing human memory CD8+ T cells survives cytotoxic chemotherapy. Immunity 31, 834-844.
96. Verbeek, S., Izon, D., Hofhuis, F., Robanus-Maandag, E., Rielete, H., van de Wetering, M., et al. (1995). An HMG-box-containing T-cell factor required for thymocyte differentiation. Nature 374, 70-74.
97. Wherry, E. J., Teichgräber, V., Becker, T. C., Masopust, D., Kaech, S. M., Antia, R., et al. (2003). Lineage relationship and protective immunity of memory CD8 T cell subsets. Nat. Immunol. 4, 225-234.
98. Williams, M. A., and Bevan, M. J. (2007). Effector and memory CTL differentiation. Annu. Rev. Immunol. 25, 171-192.
99. Williams, M. A., Tyznik, A. J., and Bevan, M. J. (2006). Interleukin-2 signals during priming are required for secondary expansion of CD8+ memory T cells. Nature 441, 890-893.
100. Willinger, T., Freeman, T., Herbert, M., Hasegawa, H., McMichael, A. J., and Callan, M. F. C. (2006). Human naive CD8 T cells down-regulate expression of the WNT pathway transcription factors lymphoid enhancer binding factor 1 and transcription factor 7 (T cell factor-1) following antigen encounter in vitro and in vivo. J. Immunol. 176, 1439-1446.
101. Wirth, T. C., Xue, H.-H., Rai, D., Sabel, J. T., Bair, T., Harty, J. T., et al. (2010). Repetitive antigen stimulation induces stepwise transcriptome diversification but preserves a core signature of memory CD8(+) T cell differentiation. Immunity 33, 128-140.
102. Xue, H.-H., and Zhao, D.-M. (2012). Regulation of mature T cell responses by the Wnt signaling pathway. Ann. N.Y. Acad. Sci. 1247, 16-33.
103. Yang, C. Y., Best, J. A., Knell, J., Yang, E., Sheridan, A. D., Jesionek, A. K., et al. (2011). The transcriptional regulators Id2 and Id3 control the formation of distinct memory CD8+ T cell subsets. Nat. Immunol. 12, 1221-1229.
104. Yi, J. S., Du, M., and Zajac, A. J. (2009). A vital role for interleukin-21 in the control of a chronic viral infection. Science 324, 1572-1576.
105. Zehn, D., Lee, S. Y., and Bevan, M. J. (2009). Complete but curtailed T-cell response to very low-affinity antigen. Nature 458, 211-214.
106. Zeng, R., Spolski, R., Finkelstein, S. E., Oh, S., Kovanen, P. E., Hinrichs, C. S., et al. (2005). Synergy of IL-21 and IL-15 in regulating CD8+ T cell expansion and function. J. Exp. Med. 201, 139-148.
107. Zhang, Y., Joe, G., Hexner, E., Zhu, J., and Emerson, S. G. (2005). Host-reactive CD8+ memory stem cells in graft-versus-host disease. Nat. Med. 11, 1299-1305.
108. Zhao, D.-M., Yu, S., Zhou, X., Haring, J. S., Held, W., Badovinac, V. P., et al. (2010). Constitutive activation of Wnt signaling favors generation of memory CD8 T cells. J. Immunol. 184, 1191-1199.
109. Zhou, X., Yu, S., Zhao, D.-M., Harty, J. T., Badovinac, V. P., and Xue, H.-H. (2010). Differentiation and persistence of memory CD8(+) T cells depend on T cell factor 1. Immunity 33, 229-240.