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The Journal of Immunology, Vol 151, Issue 5 2546-2554, Copyright © 1993 by American Association of Immunologists
ARTICLES |
DJ Veis, CL Sentman, EA Bach and SJ Korsmeyer
Department of Medicine, Howard Hughes Medical Institute, Washington University School of Medicine, St. Louis, MO 63110.
Bcl-2, a proto-oncogene that can block apoptosis, was found to be expressed throughout the thymic medulla, but in only scattered cells in the thymic cortex. In order to determine the precise distribution of Bcl-2 protein during thymocyte development, we utilized mAb specific for either mouse or human Bcl-2. Thymocyte subpopulations were assessed using three-color flow cytometry and a saponin-permeabilization method. Staining of adult mouse and human thymocytes was comparable, with 20 to 35% of cells expressing Bcl-2. Bcl-2 was expressed in nearly all CD4+ and CD8+, and CD3hi cells, but in only 5 to 10% of CD4+8+ cells. The CD4-8- population was more variable, with 25 to 40% of human cells and 65 to 80% of murine cells expressing Bcl-2. In sorted adult murine CD4- 8- cells, the very immature Pgp-1+/IL-2R alpha- subset had a high percentage of Bcl-2+ cells. Bcl-2 expression was also examined during murine fetal development. At fetal day 15.5 to 16.5, 60 to 70% of total thymocytes expressed Bcl-2. By fetal day 17.5, overall Bcl-2 expression fell to adult levels of 20 to 30%. Bcl-2 was present in peripheral T cells from lymph node, spleen, and peripheral blood at uniformly high levels. In vitro stimulation with anti-CD3 or anti-TCR antibodies increased Bcl-2 expression in total thymocyte cultures, but could not induce Bcl-2 expression in CD4+8+ cells, even with the addition of a variety of cytokines. These data suggest that early double negative thymocytes express Bcl-2 but lose Bcl-2 with differentiation to the double positive stage. Thymocytes regain Bcl-2 during selection to a single positive state and retain Bcl-2 in the periphery.
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D. J. Izon, S. Rozenfeld, S. T. Fong, L. Komuves, C. Largman, and H. J. Lawrence Loss of Function of the Homeobox Gene Hoxa-9 Perturbs Early T-Cell Development and Induces Apoptosis in Primitive Thymocytes Blood, July 15, 1998; 92(2): 383 - 393. [Abstract] [Full Text] [PDF]
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R. A. MacCorkle, K. W. Freeman, and D. M. Spencer Synthetic activation of caspases: Artificial death switches PNAS, March 31, 1998; 95(7): 3655 - 3660. [Abstract] [Full Text] [PDF]
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J. L. Gommerman and S. A. Berger Protection From Apoptosis by Steel Factor But Not Interleukin-3 Is Reversed Through Blockade of Calcium Influx Blood, March 15, 1998; 91(6): 1891 - 1900. [Abstract] [Full Text] [PDF]
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E. G. St. Clair, S. J. Anderson, and Z. N. Oltvai Bcl-2 Counters Apoptosis by Bax Heterodimerization-dependent and -independent Mechanisms in the T-cell Lineage J. Biol. Chem., November 14, 1997; 272(46): 29347 - 29355. [Abstract] [Full Text] [PDF]
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J. Kirberg, A. Berns, and H. v. Boehmer Peripheral T Cell Survival Requires Continual Ligation of the T Cell Receptor to Major Histocompatibility Complex-Encoded Molecules J. Exp. Med., October 20, 1997; 186(8): 1269 - 1275. [Abstract] [Full Text] [PDF]
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Y.-j. Lee and E. Shacter Bcl-2 Does Not Protect Burkitt's Lymphoma Cells From Oxidant-Induced Cell Death Blood, June 15, 1997; 89(12): 4480 - 4492. [Abstract] [Full Text] [PDF]
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N. L. Perillo, C. H. Uittenbogaart, J. T. Nguyen, and L. G. Baum Galectin-1, an Endogenous Lectin Produced by Thymic Epithelial Cells, Induces Apoptosis of Human Thymocytes J. Exp. Med., May 19, 1997; 185(10): 1851 - 1858. [Abstract] [Full Text] [PDF]
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V. N. Ivanov and V. N. Ivanov Transcription Factor Activation during Signal-induced Apoptosis of Immature CD4+CD8+ Thymocytes. A PROTECTIVE ROLE OF c-Fos J. Biol. Chem., March 28, 1997; 272(13): 8558 - 8566. [Abstract] [Full Text] [PDF]
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Y. Matsuzaki, K.-i. Nakayama, K. Nakayama, T. Tomita, M. Isoda, D. Y. Loh, and H. Nakauchi Role of bcl-2 in the Development of Lymphoid Cells From the Hematopoietic Stem Cell Blood, February 1, 1997; 89(3): 853 - 862. [Abstract] [Full Text] [PDF]
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H. Nakajima, E. W. Shores, M. Noguchi, and W. J. Leonard The Common Cytokine Receptor {gamma} Chain Plays an Essential Role in Regulating Lymphoid Homeostasis J. Exp. Med., January 20, 1997; 185(2): 189 - 196. [Abstract] [Full Text] [PDF]
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P. Res, B. Blom, T. Hori, K. Weijer, and H. Spits Downregulation of CD1 Marks Acquisition of Functional Maturation of Human Thymocytes and Defines a Control Point in Late Stages of Human T Cell Development J. Exp. Med., January 6, 1997; 185(1): 141 - 152. [Abstract] [Full Text] [PDF]
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J. A. Punt, H. Suzuki, L. G. Granger, S. O. Sharrow, and A. Singer Lineage Commitment in the Thymus: Only the Most Differentiated (TCRhibcl-2hi) Subset of CD4+CD8+Thymocytes Has Selectively Terminated CD4 or CD8 Synthesis J. Exp. Med., December 1, 1996; 184(6): 2091 - 2100. [Abstract] [Full Text] [PDF]
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 D Taylor, P Badiani, and K Weston A dominant interfering Myb mutant causes apoptosis in T cells. Genes & Dev., November 1, 1996; 10(21): 2732 - 2744. [Abstract] [PDF]
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M A Bogue, C Zhu, E Aguilar-Cordova, L A Donehower, and D B Roth p53 is required for both radiation-induced differentiation and rescue of V(D)J rearrangement in scid mouse thymocytes. Genes & Dev., March 1, 1996; 10(5): 553 - 565. [Abstract] [PDF]
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 D. Merry, D. Veis, W. Hickey, and S. Korsmeyer bcl-2 protein expression is widespread in the developing nervous system and retained in the adult PNS Development, January 2, 1994; 120(2): 301 - 311. [Abstract] [PDF]
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 S. Cory, A. Strasser, T. Jacks, L.M. Corcoran, T. Metz, A.W. Harris, and J.M. Adams Enhanced Cell Survival and Tumorigenesis Cold Spring Harb Symp Quant Biol, January 1, 1994; 59(0): 365 - 375. [Abstract] [PDF]
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X.-M. Yin, Z.N. Oltvai, D.J. Veis-Novack, G.P. Linette, and S.J. Korsmeyer Bcl-2 Gene Family and the Regulation of Programmed Cell Death Cold Spring Harb Symp Quant Biol, January 1, 1994; 59(0): 387 - 393. [Abstract] [PDF]
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S. Tsujino, J. P. Di Santo, A. Takaoka, T. L. McKernan, S. Noguchi, C. Taya, H. Yonekawa, T. Saito, T. Taniguchi, and H. Fujii Differential requirement of the cytoplasmic subregions of gamma c chain in T cell development and function PNAS, September 12, 2000; 97(19): 10514 - 10519. [Abstract] [Full Text] [PDF]
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