| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Immunology Research Division, Department of Pathology, Brigham & Women’s Hospital and Harvard Medical School, Boston, Ma 02115
Apoptotic cell death is an important mechanism for maintaining homeostasis in the immune system and for regulating the fates of lymphocytes following encounters with self and foreign Ags. To study the physiologic roles of the proapoptotic Fas pathway and the antiapoptotic protein, Bcl-2, in T cell maturation and homeostasis, a TCR transgene has been bred into mice lacking functional Fas and mice that express Bcl-2 constitutively. In vitro, Fas-deficient T cells are resistant to activation-induced cell death, whereas Bcl-2-overexpressing T cells are resistant to death induced by withdrawal of growth factors. In vivo, Bcl-2-overexpressing mice accumulate T cells in the thymus and peripheral lymphoid tissues in the absence of Ag, but these cells are deleted normally after Ag administration. In contrast, Fas-deficient mature T cells are present in normal numbers in the absence of Ag, but are resistant to Ag-induced deletion. Both Fas-deficient and Bcl-2 overexpressing thymocytes are deleted when exposed to transgene-encoded circulating self Ag, indicating that the pathways of apoptosis controlled by these proteins are not critical for negative selection of developing thymocytes. Moreover, deficiency of Fas, but not Bcl-2 overexpression, results in the accumulation of autoreactive T cells in peripheral lymphoid tissues. These results demonstrate that Fas and Bcl-2 regulate different pathways of apoptosis that may serve distinct functions in lymphocyte homeostasis and in the maintenance of T cell tolerance.
This article has been cited by other articles:
|
|
 |
|
  S. Fountoulakis, G. Vartholomatos, N. Kolaitis, S. Frillingos, G. Philippou, and A. Tsatsoulis Differential expression of Fas system apoptotic molecules in peripheral lymphocytes from patients with Graves' disease and Hashimoto's thyroiditis. Eur. J. Endocrinol., June 1, 2008; 158(6): 853 - 859. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. L. Redmond, C.-H. Wei, H. T. C. Kreuwel, and L. A. Sherman The Apoptotic Pathway Contributing to the Deletion of Naive CD8 T Cells during the Induction of Peripheral Tolerance to a Cross-Presented Self-Antigen J. Immunol., April 15, 2008; 180(8): 5275 - 5282. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Mittal, S. Papa, G. Franzoso, and R. Sen NF-{kappa}B-Dependent Regulation of the Timing of Activation-Induced Cell Death of T Lymphocytes J. Immunol., February 15, 2006; 176(4): 2183 - 2189. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Bahri, F. Hirsch, A. Josse, N. Rouas-Freiss, N. Bidere, A. Vasquez, E. D. Carosella, B. Charpentier, and A. Durrbach Soluble HLA-G Inhibits Cell Cycle Progression in Human Alloreactive T Lymphocytes J. Immunol., February 1, 2006; 176(3): 1331 - 1339. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K W Chan, P Y Lee, A K Y Lam, S Law, J Wong, and G Srivastava Clinical relevance of Fas expression in oesophageal squamous cell carcinoma J. Clin. Pathol., January 1, 2006; 59(1): 101 - 104. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. M. Levy, O. Gilad, L. Xia, Y. Izumiya, J. Choi, A. Tsalenko, Z. Yakhini, R. Witter, L. Lee, C. J. Cardona, et al. Marek's disease virus Meq transforms chicken cells via the v-Jun transcriptional cascade: A converging transforming pathway for avian oncoviruses PNAS, October 11, 2005; 102(41): 14831 - 14836. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Cebecauer, P. Guillaume, P. Hozak, S. Mark, H. Everett, P. Schneider, and I. F. Luescher Soluble MHC-Peptide Complexes Induce Rapid Death of CD8+ CTL J. Immunol., June 1, 2005; 174(11): 6809 - 6819. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. Cao, Y. Xia, M. Azadniv, and I. N. Crispe The E2F-1 Transcription Factor Promotes Caspase-8 and Bid Expression, and Enhances Fas Signaling in T Cells J. Immunol., July 15, 2004; 173(2): 1111 - 1117. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Pandiyan, D. Gartner, O. Soezeri, A. Radbruch, K. Schulze-Osthoff, and M. C. Brunner-Weinzierl CD152 (CTLA-4) Determines the Unequal Resistance of Th1 and Th2 Cells against Activation-induced Cell Death by a Mechanism Requiring PI3 Kinase Function J. Exp. Med., March 15, 2004; 199(6): 831 - 842. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. I. Rutitzky, G. A. Mirkin, and M. J. Stadecker Apoptosis by Neglect of CD4+ Th Cells in Granulomas: A Novel Effector Mechanism Involved in the Control of Egg-Induced Immunopathology in Murine Schistosomiasis J. Immunol., August 15, 2003; 171(4): 1859 - 1867. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. V. Denis, Q. Yu, P. Ma, L. Deeds, D. V. Faller, and C.-Y. Chen Bcl-2, via Its BH4 Domain, Blocks Apoptotic Signaling Mediated by Mitochondrial Ras J. Biol. Chem., February 14, 2003; 278(8): 5775 - 5785. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. Tang, J. A. Smith, G. L. Szot, P. Zhou, M.-L. Alegre, K. J. Henriksen, C. B. Thompson, and J. A. Bluestone CD28/B7 Regulation of Anti-CD3-Mediated Immunosuppression In Vivo J. Immunol., February 1, 2003; 170(3): 1510 - 1516. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Ayala, C.-S. Chung, J. L. Lomas, G. Y. Song, L. A. Doughty, S. H. Gregory, W. G. Cioffi, B. W. LeBlanc, J. Reichner, H. H. Simms, et al. Shock-Induced Neutrophil Mediated Priming for Acute Lung Injury in Mice: Divergent Effects of TLR-4 and TLR-4/FasL Deficiency Am. J. Pathol., December 1, 2002; 161(6): 2283 - 2294. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Refaeli, L. Van Parijs, S. I. Alexander, and A. K. Abbas Interferon {gamma} Is Required for Activation-induced Death of T Lymphocytes J. Exp. Med., October 7, 2002; 196(7): 999 - 1005. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. R. Drobyski, R. Komorowski, B. Logan, and M. Gendelman Role of the Passive Apoptotic Pathway in Graft-Versus-Host Disease J. Immunol., August 1, 2002; 169(3): 1626 - 1633. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Melis, L. Siena, E. Pace, M. Gjomarkaj, M. Profita, A. Pirazzoli, M. Todaro, G. Stassi, G. Bonsignore, and A.M. Vignola Fluticasone induces apoptosis in peripheral T-lymphocytes: a comparison between asthmatic and normal subjects Eur. Respir. J., February 1, 2002; 19(2): 257 - 266. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Kelly, A. Won, Y. Refaeli, and L. V. Parijs IL-2 and Related Cytokines Can Promote T Cell Survival by Activating AKT J. Immunol., January 15, 2002; 168(2): 597 - 603. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T.-S. Wu, J.-M. Lee, Y.-G. Lai, J.-C. Hsu, C.-Y. Tsai, Y.-H. Lee, and N.-S. Liao Reduced Expression of Bcl-2 in CD8+ T Cells Deficient in the IL-15 Receptor {alpha}-Chain J. Immunol., January 15, 2002; 168(2): 705 - 712. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. J. Fry, B. L. Christensen, K. L. Komschlies, R. E. Gress, and C. L. Mackall Interleukin-7 restores immunity in athymic T-cell-depleted hosts Blood, March 15, 2001; 97(6): 1525 - 1533. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Wekerle, J. Kurtz, M. H. Sayegh, H. Ito, A. D. Wells, S. Bensinger, J. Shaffer, L. A. Turka, and M. Sykes Peripheral Deletion After Bone Marrow Transplantation with Costimulatory Blockade Has Features of Both Activation-Induced Cell Death and Passive Cell Death J. Immunol., February 15, 2001; 166(4): 2311 - 2316. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C.-H. Wei, H. Yagita, M. G. Masucci, and V. Levitsky Different Programs of Activation-Induced Cell Death Are Triggered in Mature Activated CTL by Immunogenic and Partially Agonistic Peptide Ligands J. Immunol., January 15, 2001; 166(2): 989 - 995. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. N. Shi, H. Y. Liu, and C. Nagler-Anderson Enteric Infection Acts as an Adjuvant for the Response to a Model Food Antigen J. Immunol., December 1, 2000; 165(11): 6174 - 6182. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Majlessi and G. Bordenave Non-overlapping Fas- and BCL-2-regulated death pathways in IgG2ab-producing B cells Int. Immunol., July 1, 2000; 12(7): 969 - 976. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J. Pinkoski, T. Brunner, D. R. Green, and T. Lin Fas and Fas ligand in gut and liver Am J Physiol Gastrointest Liver Physiol, March 1, 2000; 278(3): G354 - G366. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. J. Hamann, J. E. Vieira, A. J. Halayko, D. Dorscheid, S. R. White, S. M. Forsythe, B. Camoretti-Mercado, K. F. Rabe, and J. Solway Fas cross-linking induces apoptosis in human airway smooth muscle cells Am J Physiol Lung Cell Mol Physiol, March 1, 2000; 278(3): L618 - L624. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Newton and A. Strasser Ionizing Radiation and Chemotherapeutic Drugs Induce Apoptosis in Lymphocytes in the Absence of Fas or FADD/MORT1 Signaling: Implications for Cancer Therapy J. Exp. Med., January 3, 2000; 191(1): 195 - 200. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Schwarting, G. Tesch, K. Kinoshita, R. Maron, H. L. Weiner, and V. R. Kelley IL-12 Drives IFN-{gamma}-Dependent Autoimmune Kidney Disease in MRL-Faslpr Mice J. Immunol., December 15, 1999; 163(12): 6884 - 6891. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Van Molle, G. Denecker, I. Rodriguez, P. Brouckaert, P. Vandenabeele, and C. Libert Activation of Caspases in Lethal Experimental Hepatitis and Prevention by Acute Phase Proteins J. Immunol., November 15, 1999; 163(10): 5235 - 5241. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. D. Milner, S. C. Kent, T. A. Ashley, S. B. Wilson, J. L. Strominger, and D. A. Hafler Differential Responses of Invariant V{alpha}24J{alpha}Q T Cells and MHC Class II-Restricted CD4+ T Cells to Dexamethasone J. Immunol., September 1, 1999; 163(5): 2522 - 2529. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. C. Hebib, O. Deas, M. Rouleau, A. Durrbach, B. Charpentier, F. Beaujean, J.-P. Vernant, and A. Senik Peripheral Blood T Cells Generated After Allogeneic Bone Marrow Transplantation: Lower Levels of Bcl-2 Protein and Enhanced Sensitivity to Spontaneous and CD95-Mediated Apoptosis In Vitro. Abrogation of the Apoptotic Phenotype Coincides With the Recovery of Normal Naive/Primed T-Cell Profiles Blood, September 1, 1999; 94(5): 1803 - 1813. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Brochu, B. Rioux-Masse, J. Roy, D.-C. Roy, and C. Perreault Massive Activation-Induced Cell Death of Alloreactive T Cells With Apoptosis of Bystander Postthymic T Cells Prevents Immune Reconstitution in Mice With Graft-Versus-Host Disease Blood, July 15, 1999; 94(2): 390 - 400. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. GUDMUNDSDOTTIR and L. A. TURKA T Cell Costimulatory Blockade: New Therapies for TransplantRejection J. Am. Soc. Nephrol., June 1, 1999; 10(6): 1356 - 1365. [Abstract] [Full Text]
|
|
|
|
|
|
M. M. Di Somma, F. Somma, M. S. G. Montani, R. Mangiacasale, E. Cundari, and E. Piccolella TCR Engagement Regulates Differential Responsiveness of Human Memory T Cells to Fas (CD95)-Mediated Apoptosis J. Immunol., April 1, 1999; 162(7): 3851 - 3858. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y.-C. Lim, L. Henault, A. J. Wagers, G. S. Kansas, F. W. Luscinskas, and A. H. Lichtman Expression of Functional Selectin Ligands on Th Cells Is Differentially Regulated by IL-12 and IL-4 J. Immunol., March 15, 1999; 162(6): 3193 - 3201. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C.-L. Chu, S.-S. Chen, T.-S. Wu, S.-C. Kuo, and N.-S. Liao Differential Effects of IL-2 and IL-15 on the Death and Survival of Activated TCR{gamma}{delta}+ Intestinal Intraepithelial Lymphocytes J. Immunol., February 15, 1999; 162(4): 1896 - 1903. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
