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Institute for Experimental Immunology, University Hospital Zürich, Zürich, Switzerland
Phenotypically and functionally, the early steps of T cell differentiation are not well characterized. In addition, the effector T cell stage shares several phenotypic characteristics with memory T cells, which has made the analysis of T cell memory difficult. In this study, we have investigated in vitro and in vivo the differentiation of naive CTL into effector and memory CTL as a function of cell division using lymphocytic choriomeningitis virus-specific TCR-transgenic spleen cells labeled with the vital dye carboxyfluorescein diacetate, succinimidyl ester. The following major points emerged. 1) During the first nine cell divisions, the investigated cell surface markers were strongly modulated. 2) The TCR was stepwise down-regulated during viral infection. 3) Cytotoxic effector function was acquired within one cell division and was retained during the next four to five divisions. 4) In vitro, CTL reached a CD44highCD62L+ memory phenotype after 6–10 cell divisions and required restimulation to exert effector function. 5) Lymphocytic choriomeningitis virus memory mice contained two distinct memory populations: a CD44highCD62L- population, predominately located in the spleen and exerting rapid effector function, and a CD44highCD62L+ population found in the spleen and the lymph nodes, which had lost immediate effector function. This finding suggests that two types of memory CTL exist. The correlation between CD62L expression, effector function, and Ag persistence is discussed.
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K. Haglund, I. Leiner, K. Kerksiek, L. Buonocore, E. Pamer, and J. K. Rose Robust Recall and Long-Term Memory T-Cell Responses Induced by Prime-Boost Regimens with Heterologous Live Viral Vectors Expressing Human Immunodeficiency Virus Type 1 Gag and Env Proteins J. Virol., June 27, 2002; 76(15): 7506 - 7517. [Abstract] [Full Text] [PDF]
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S. P. Li, Z. Cai, W. Shi, A. Brunmark, M. Jackson, and P.-J. Linton Early Antigen-Specific Response by Naive CD8 T Cells Is Not Altered with Aging J. Immunol., June 15, 2002; 168(12): 6120 - 6127. [Abstract] [Full Text] [PDF]
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S. N. Mueller, C. M. Jones, C. M. Smith, W. R. Heath, and F. R. Carbone Rapid Cytotoxic T Lymphocyte Activation Occurs in the Draining Lymph Nodes After Cutaneous Herpes Simplex Virus Infection as a Result of Early Antigen Presentation and Not the Presence of Virus J. Exp. Med., March 4, 2002; 195(5): 651 - 656. [Abstract] [Full Text] [PDF]
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R. M. Coles, S. N. Mueller, W. R. Heath, F. R. Carbone, and A. G. Brooks Progression of Armed CTL from Draining Lymph Node to Spleen Shortly After Localized Infection with Herpes Simplex Virus 1 J. Immunol., January 15, 2002; 168(2): 834 - 838. [Abstract] [Full Text] [PDF]
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M. J. Estcourt, A. J. Ramsay, A. Brooks, S. A. Thomson, C. J. Medveckzy, and I. A. Ramshaw Prime-boost immunization generates a high frequency, high-avidity CD8+ cytotoxic T lymphocyte population Int. Immunol., January 1, 2002; 14(1): 31 - 37. [Abstract] [Full Text] [PDF]
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W. Weninger, M. A. Crowley, N. Manjunath, and U. H. von Andrian Migratory Properties of Naive, Effector, and Memory CD8+ T Cells J. Exp. Med., October 1, 2001; 194(7): 953 - 966. [Abstract] [Full Text] [PDF]
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K. Sato, Y. Torimoto, Y. Tamura, M. Shindo, H. Shinzaki, K. Hirai, and Y. Kohgo Immunotherapy using heat-shock protein preparations of leukemia cells after syngeneic bone marrow transplantation in mice Blood, September 15, 2001; 98(6): 1852 - 1857. [Abstract] [Full Text] [PDF]
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J. Hernandez, S. Aung, W. L. Redmond, and L. A. Sherman Phenotypic and Functional Analysis of CD8+ T Cells Undergoing Peripheral Deletion in Response to Cross-Presentation of Self-Antigen J. Exp. Med., September 10, 2001; 194(6): 707 - 718. [Abstract] [Full Text] [PDF]
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J. P. Medema, D. H. Schuurhuis, D. Rea, J. van Tongeren, J. de Jong, S. A. Bres, S. Laban, R. E.M. Toes, M. Toebes, T. N.M. Schumacher, et al. Expression of the Serpin Serine Protease Inhibitor 6 Protects Dendritic Cells from Cytotoxic T Lymphocyte-induced Apoptosis: Differential Modulation by T Helper Type 1 and Type 2 Cells J. Exp. Med., September 4, 2001; 194(5): 657 - 668. [Abstract] [Full Text] [PDF]
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 Y. Kudo, C A R Boyd, I L Sargent, and C W G Redman Tryptophan degradation by human placental indoleamine 2,3-dioxygenase regulates lymphocyte proliferation J. Physiol., August 15, 2001; 535(1): 207 - 215. [Abstract] [Full Text] [PDF]
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J. K. Sandberg, N. M. Fast, and D. F. Nixon Functional Heterogeneity of Cytokines and Cytolytic Effector Molecules in Human CD8+ T Lymphocytes J. Immunol., July 1, 2001; 167(1): 181 - 187. [Abstract] [Full Text] [PDF]
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J. M. Faint, N. E. Annels, S. J. Curnow, P. Shields, D. Pilling, A. D. Hislop, L. Wu, A. N. Akbar, C. D. Buckley, P. A. H. Moss, et al. Memory T Cells Constitute a Subset of the Human CD8+CD45RA+ Pool with Distinct Phenotypic and Migratory Characteristics J. Immunol., July 1, 2001; 167(1): 212 - 220. [Abstract] [Full Text] [PDF]
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N. Auphan-Anezin and A.-M. Schmitt-Verhulst Differential Survival of Transferred CD8 T Cells and Host Reconstitution Depending on TCR Avidity for Host-Expressed Alloantigen J. Immunol., June 15, 2001; 166(12): 7200 - 7207. [Abstract] [Full Text] [PDF]
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D. J. Nelson, S. Mukherjee, C. Bundell, S. Fisher, D. van Hagen, and B. Robinson Tumor Progression Despite Efficient Tumor Antigen Cross-Presentation and Effective "Arming" of Tumor Antigen-Specific CTL J. Immunol., May 1, 2001; 166(9): 5557 - 5566. [Abstract] [Full Text] [PDF]
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R. J. Hogan, E. J. Usherwood, W. Zhong, A. D. Roberts, R. W. Dutton, A. G. Harmsen, and D. L. Woodland Activated Antigen-Specific CD8+ T Cells Persist in the Lungs Following Recovery from Respiratory Virus Infections J. Immunol., February 1, 2001; 166(3): 1813 - 1822. [Abstract] [Full Text] [PDF]
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M. Ahmadzadeh, S. F. Hussain, and D. L. Farber Heterogeneity of the Memory CD4 T Cell Response: Persisting Effectors and Resting Memory T Cells J. Immunol., January 15, 2001; 166(2): 926 - 935. [Abstract] [Full Text] [PDF]
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K. Izeradjene, J.-P. Revillard, and L. Genestier Inhibition of thymidine synthesis by folate analogues induces a Fas-Fas ligand-independent deletion of superantigen-reactive peripheral T cells Int. Immunol., January 1, 2001; 13(1): 85 - 93. [Abstract] [Full Text] [PDF]
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H. Yamada, G. Matsuzaki, Y. Iwamoto, and K. Nomoto Unusual cytotoxic activities of thymus-independent, self-antigen-specific CD8+ T cells Int. Immunol., December 1, 2000; 12(12): 1677 - 1683. [Abstract] [Full Text] [PDF]
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A. L. Marzo, B. F. Kinnear, R. A. Lake, J. J. Frelinger, E. J. Collins, B. W. S. Robinson, and B. Scott Tumor-Specific CD4+ T Cells Have a Major ""Post-Licensing"" Role in CTL Mediated Anti-Tumor Immunity J. Immunol., December 1, 2000; 165(11): 6047 - 6055. [Abstract] [Full Text] [PDF]
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D. Nelson, C. Bundell, and B. Robinson In Vivo Cross-Presentation of a Soluble Protein Antigen: Kinetics, Distribution, and Generation of Effector CTL Recognizing Dominant and Subdominant Epitopes J. Immunol., December 1, 2000; 165(11): 6123 - 6132. [Abstract] [Full Text] [PDF]
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I. Apostolou, A. Cumano, G. Gachelin, and P. Kourilsky Evidence for Two Subgroups of CD4-CD8- NKT Cells with Distinct TCR{alpha}{beta} Repertoires and Differential Distribution in Lymphoid Tissues J. Immunol., September 1, 2000; 165(5): 2481 - 2490. [Abstract] [Full Text] [PDF]
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B. K. Cho, V. P. Rao, Q. Ge, H. N. Eisen, and J. Chen Homeostasis-stimulated Proliferation Drives Naive T Cells to Differentiate Directly into Memory T Cells J. Exp. Med., August 21, 2000; 192(4): 549 - 556. [Abstract] [Full Text] [PDF]
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K. Murali-Krishna and R. Ahmed Cutting Edge: Naive T Cells Masquerading as Memory Cells J. Immunol., August 15, 2000; 165(4): 1733 - 1737. [Abstract] [Full Text] [PDF]
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H. Andersen, D. Dempsey, R. Chervenak, and S. R. Jennings Expression of Intracellular IFN-{gamma} in HSV-1-Specific CD8+ T Cells Identifies Distinct Responding Subpopulations During the Primary Response to Infection J. Immunol., August 15, 2000; 165(4): 2101 - 2107. [Abstract] [Full Text] [PDF]
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P. Bousso, F. Lemaitre, J. Bilsborough, and P. Kourilsky Facing Two T Cell Epitopes: A Degree of Randomness in the Primary Response Is Lost Upon Secondary Immunization J. Immunol., July 15, 2000; 165(2): 760 - 767. [Abstract] [Full Text] [PDF]
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S. Gasser, P. Corthesy, F. Beerman, H. R. MacDonald, and M. Nabholz Constitutive Expression of a Chimeric Receptor That Delivers IL-2/IL-15 Signals Allows Antigen-Independent Proliferation of CD8+CD44high But Not Other T Cells J. Immunol., June 1, 2000; 164(11): 5659 - 5667. [Abstract] [Full Text] [PDF]
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T. J. Dengler and J. S. Pober Human Vascular Endothelial Cells Stimulate Memory But Not Naive CD8+ T Cells to Differentiate into CTL Retaining an Early Activation Phenotype J. Immunol., May 15, 2000; 164(10): 5146 - 5155. [Abstract] [Full Text] [PDF]
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D. Wodarz, R. M. May, and M. A. Nowak The role of antigen-independent persistence of memory cytotoxic T lymphocytes Int. Immunol., April 1, 2000; 12(4): 467 - 477. [Abstract] [Full Text] [PDF]
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I. F. Hermans, D. S. Ritchie, J. Yang, J. M. Roberts, and F. Ronchese CD8+ T Cell-Dependent Elimination of Dendritic Cells In Vivo Limits the Induction of Antitumor Immunity J. Immunol., March 15, 2000; 164(6): 3095 - 3101. [Abstract] [Full Text] [PDF]
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