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CUTTING EDGE |
Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322
This study shows that naive CD8 T cells can acquire characteristics of memory T cells in the absence of stimulation with specific Ag simply by the process of homeostatic proliferation under lymphopenic conditions. This Ag-independent T cell differentiation pathway did not result in up-regulation of early activation markers (CD69, CD25, CD71), but expression of several memory markers (CD44, CD122, Ly6C) increased progressively with successive divisions. These markers were then stably expressed, and these cells also became more responsive functionally to specific Ag. Thus, all "memory" phenotype T cells in an individual may not be true Ag-experienced cells and may include naive cells masquerading as memory cells. These findings are specially relevant in cases of disease or treatment-induced lymphopenia such as in HIV-infected individuals or transplant recipients. In addition, this study may have implications for autoimmunity because homeostatic proliferation of naive T cells requires interaction with self peptide plus MHC molecules.
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I. Messaoudi, J. Warner, D. Nikolich-Zugich, M. Fischer, and J. Nikolich-Zugich Molecular, Cellular, and Antigen Requirements for Development of Age-Associated T Cell Clonal Expansions In Vivo J. Immunol., January 1, 2006; 176(1): 301 - 308. [Abstract] [Full Text] [PDF]
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R. Nishikomori, H. Akutagawa, K. Maruyama, M. Nakata-Hizume, K. Ohmori, K. Mizuno, A. Yachie, T. Yasumi, T. Kusunoki, T. Heike, et al. X-linked ectodermal dysplasia and immunodeficiency caused by reversion mosaicism of NEMO reveals a critical role for NEMO in human T-cell development and/or survival Blood, June 15, 2004; 103(12): 4565 - 4572. [Abstract] [Full Text] [PDF]
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Y. Zhang, G. Joe, J. Zhu, R. Carroll, B. Levine, E. Hexner, C. June, and S. G. Emerson Dendritic cell-activated CD44hiCD8+ T cells are defective in mediating acute graft-versus-host disease but retain graft-versus-leukemia activity Blood, May 15, 2004; 103(10): 3970 - 3978. [Abstract] [Full Text] [PDF]
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M. Koschella, D. Voehringer, and H. Pircher CD40 Ligation In Vivo Induces Bystander Proliferation of Memory Phenotype CD8 T Cells J. Immunol., April 15, 2004; 172(8): 4804 - 4811. [Abstract] [Full Text] [PDF]
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B. Min, G. Foucras, M. Meier-Schellersheim, and W. E. Paul Spontaneous proliferation, a response of naive CD4 T cells determined by the diversity of the memory cell repertoire PNAS, March 16, 2004; 101(11): 3874 - 3879. [Abstract] [Full Text] [PDF]
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Q. Ge, A. Bai, B. Jones, H. N. Eisen, and J. Chen Competition for self-peptide-MHC complexes and cytokines between naive and memory CD8+ T cells expressing the same or different T cell receptors PNAS, March 2, 2004; 101(9): 3041 - 3046. [Abstract] [Full Text] [PDF]
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A. Khanolkar, M. J. Fuller, and A. J. Zajac CD4 T Cell-Dependent CD8 T Cell Maturation J. Immunol., March 1, 2004; 172(5): 2834 - 2844. [Abstract] [Full Text] [PDF]
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L. M. Piliero, A. N. Sanford, D. M. McDonald-McGinn, E. H. Zackai, and K. E. Sullivan T-cell homeostasis in humans with thymic hypoplasia due to chromosome 22q11.2 deletion syndrome Blood, February 1, 2004; 103(3): 1020 - 1025. [Abstract] [Full Text] [PDF]
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T. Schuler, G. J. Hammerling, and B. Arnold Cutting Edge: IL-7-Dependent Homeostatic Proliferation of CD8+ T Cells in Neonatal Mice Allows the Generation of Long-Lived Natural Memory T Cells J. Immunol., January 1, 2004; 172(1): 15 - 19. [Abstract] [Full Text] [PDF]
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W. L. Redmond, J. Hernandez, and L. A. Sherman Deletion of Naive CD8 T Cells Requires Persistent Antigen and Is Not Programmed by an Initial Signal from the Tolerogenic APC J. Immunol., December 15, 2003; 171(12): 6349 - 6354. [Abstract] [Full Text] [PDF]
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B. Bellier, V. Thomas-Vaslin, M.-F. Saron, and D. Klatzmann Turning immunological memory into amnesia by depletion of dividing T cells PNAS, December 9, 2003; 100(25): 15017 - 15022. [Abstract] [Full Text] [PDF]
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K. Benlhassan-Chahour, C. Penit, V. Dioszeghy, F. Vasseur, G. Janvier, Y. Riviere, N. Dereuddre-Bosquet, D. Dormont, R. Le Grand, and B. Vaslin Kinetics of Lymphocyte Proliferation during Primary Immune Response in Macaques Infected with Pathogenic Simian Immunodeficiency Virus SIVmac251: Preliminary Report of the Effect of Early Antiviral Therapy J. Virol., December 1, 2003; 77(23): 12479 - 12493. [Abstract] [Full Text] [PDF]
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S. E. Kerry, J. Buslepp, L. A. Cramer, R. Maile, L. L. Hensley, A. I. Nielsen, P. Kavathas, B. J. Vilen, E. J. Collins, and J. A. Frelinger Interplay between TCR Affinity and Necessity of Coreceptor Ligation: High-Affinity Peptide-MHC/TCR Interaction Overcomes Lack of CD8 Engagement J. Immunol., November 1, 2003; 171(9): 4493 - 4503. [Abstract] [Full Text] [PDF]
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I. Grandjean, L. Duban, E. A. Bonney, E. Corcuff, J. P. Di Santo, P. Matzinger, and O. Lantz Are Major Histocompatibility Complex Molecules Involved in the Survival of Naive CD4+ T Cells? J. Exp. Med., October 6, 2003; 198(7): 1089 - 1102. [Abstract] [Full Text] [PDF]
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N. L. Alves, B. Hooibrink, F. A. Arosa, and R. A. W. van Lier IL-15 induces antigen-independent expansion and differentiation of human naive CD8+ T cells in vitro Blood, October 1, 2003; 102(7): 2541 - 2546. [Abstract] [Full Text] [PDF]
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S. O. Andreasen, A. R. Thomsen, V. E. Koteliansky, T. I. Novobrantseva, A. G. Sprague, A. R. de Fougerolles, and J. P. Christensen Expression and Functional Importance of Collagen-Binding Integrins, {alpha}1{beta}1 and {alpha}2{beta}1, on Virus-Activated T Cells J. Immunol., September 15, 2003; 171(6): 2804 - 2811. [Abstract] [Full Text] [PDF]
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C. H. Maris, J. D. Miller, J. D. Altman, and J. Jacob A Transgenic Mouse Model Genetically Tags All Activated CD8 T Cells J. Immunol., September 1, 2003; 171(5): 2393 - 2401. [Abstract] [Full Text] [PDF]
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S. Ilangumaran, S. Ramanathan, J. La Rose, P. Poussier, and R. Rottapel Suppressor of Cytokine Signaling 1 Regulates IL-15 Receptor Signaling in CD8+CD44high Memory T Lymphocytes J. Immunol., September 1, 2003; 171(5): 2435 - 2445. [Abstract] [Full Text] [PDF]
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C. D. Peacock, S.-K. Kim, and R. M. Welsh Attrition of Virus-Specific Memory CD8+ T Cells During Reconstitution of Lymphopenic Environments J. Immunol., July 15, 2003; 171(2): 655 - 663. [Abstract] [Full Text] [PDF]
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Z. Kurepa, J. Su, and J. Forman Memory Phenotype of CD8+ T Cells in MHC Class Ia-Deficient Mice J. Immunol., June 1, 2003; 170(11): 5414 - 5420. [Abstract] [Full Text] [PDF]
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J. Geginat, A. Lanzavecchia, and F. Sallusto Proliferation and differentiation potential of human CD8+ memory T-cell subsets in response to antigen or homeostatic cytokines Blood, June 1, 2003; 101(11): 4260 - 4266. [Abstract] [Full Text] [PDF]
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H. I. McFarland, S. A. Hansal, D. I. Morris, D. W. McVicar, P. E. Love, and A. S. Rosenberg Signaling through MHC in transgenic mice generates a population of memory phenotype cytolytic cells that lack TCR Blood, June 1, 2003; 101(11): 4520 - 4528. [Abstract] [Full Text] [PDF]
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B. Martin, C. Bourgeois, N. Dautigny, and B. Lucas On the role of MHC class II molecules in the survival and lymphopenia-induced proliferation of peripheral CD4+ T cells PNAS, May 13, 2003; 100(10): 6021 - 6026. [Abstract] [Full Text] [PDF]
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J. M. Brenchley, N. J. Karandikar, M. R. Betts, D. R. Ambrozak, B. J. Hill, L. E. Crotty, J. P. Casazza, J. Kuruppu, S. A. Migueles, M. Connors, et al. Expression of CD57 defines replicative senescence and antigen-induced apoptotic death of CD8+ T cells Blood, April 1, 2003; 101(7): 2711 - 2720. [Abstract] [Full Text] [PDF]
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J. M. Blander, D. B. Sant'Angelo, D. Metz, S.-W. Kim, R. A. Flavell, K. Bottomly, and C. A. Janeway Jr. A Pool of Central Memory-Like CD4 T Cells Contains Effector Memory Precursors J. Immunol., March 15, 2003; 170(6): 2940 - 2948. [Abstract] [Full Text] [PDF]
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T. J. Fry, M. Moniuszko, S. Creekmore, S. J. Donohue, D. C. Douek, S. Giardina, T. T. Hecht, B. J. Hill, K. Komschlies, J. Tomaszewski, et al. IL-7 therapy dramatically alters peripheral T-cell homeostasis in normal and SIV-infected nonhuman primates Blood, March 15, 2003; 101(6): 2294 - 2299. [Abstract] [Full Text] [PDF]
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C. Sharp, C. Thompson, E. T. Samy, R. Noelle, and K. S. K. Tung CD40 Ligand in Pathogenesis of Autoimmune Ovarian Disease of Day 3-Thymectomized Mice: Implication for CD40 Ligand Antibody Therapy J. Immunol., February 15, 2003; 170(4): 1667 - 1674. [Abstract] [Full Text] [PDF]
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K. M. Kerksiek, A. Ploss, I. Leiner, D. H. Busch, and E. G. Pamer H2-M3-Restricted Memory T Cells: Persistence and Activation Without Expansion J. Immunol., February 15, 2003; 170(4): 1862 - 1869. [Abstract] [Full Text] [PDF]
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I. Jaakkola, M. Merinen, S. Jalkanen, and A. Hanninen Ly6C Induces Clustering of LFA-1 (CD11a/CD18) and Is Involved in Subtype-Specific Adhesion of CD8 T Cells J. Immunol., February 1, 2003; 170(3): 1283 - 1290. [Abstract] [Full Text] [PDF]
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