| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Howard Hughes Medical Institute and Department of Immunology, University of Washington, School of Medicine, Seattle, WA 98195
TCR-self peptide:MHC interactions play a critical role in thymic positive selection, yet relatively little is known of their function in the periphery. It has been suggested that continued contact with selecting MHC molecules is necessary for long-term peripheral maintenance of naive T cells. More recent studies have also demonstrated a role for specific self peptide:MHC complexes in the homeostatic expansion of naive T cells in lymphopenic mice. Our examination of these processes revealed that, whereas self class II MHC molecules do have a modest effect on long-term survival of individual CD4+ T cells, interactions with specific TCR ligands are not required for peripheral naive CD4+ T cell maintenance. In contrast, selective engagement of TCRs by self-peptide:MHC complexes does promote proliferation of CD4+ T cells under severe lymphopenic conditions, and this division is associated with an activation marker phenotype that is different from that induced by antigenic stimulation. Importantly, however, the ability of naive T cells to divide in response to homeostatic stimuli does not appear to be stringently dependent on TCR-self peptide:MHC interactions. Therefore, these results show that the factors regulating survival and homeostatic expansion of naive T cells in the periphery are not identical. In addition, we provide evidence for a novel form of T cell proliferation that can occur independently of TCR signaling and suggest that this reflects another mechanism regulating homeostatic T cell expansion.
This article has been cited by other articles:
|
|
 |
|
  K. Takada and S. C. Jameson Self-class I MHC molecules support survival of naive CD8 T cells, but depress their functional sensitivity through regulation of CD8 expression levels J. Exp. Med., September 28, 2009; 206(10): 2253 - 2269. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Wang, X. Chang, V. Facchinetti, Y. Zhuang, and B. Su MEKK3 Is Essential for Lymphopenia-Induced T Cell Proliferation and Survival J. Immunol., March 15, 2009; 182(6): 3597 - 3608. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Li, E. J. Gowans, C. Chougnet, M. Plebanski, and U. Dittmer Natural Regulatory T Cells and Persistent Viral Infection J. Virol., January 1, 2008; 82(1): 21 - 30. [Full Text] [PDF]
|
|
|
|
 |
|
 K. Rezvani, A. S. M. Yong, B. N. Savani, S. Mielke, K. Keyvanfar, E. Gostick, D. A. Price, D. C. Douek, and A. J. Barrett Graft-versus-leukemia effects associated with detectable Wilms tumor-1 specific T lymphocytes after allogeneic stem-cell transplantation for acute lymphoblastic leukemia Blood, September 15, 2007; 110(6): 1924 - 1932. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. De Riva, C. Bourgeois, G. Kassiotis, and B. Stockinger Noncognate Interaction with MHC Class II Molecules Is Essential for Maintenance of T Cell Metabolism to Establish Optimal Memory CD4 T Cell Function J. Immunol., May 1, 2007; 178(9): 5488 - 5495. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Shklovskaya and B. Fazekas de St. Groth Severely Impaired Clonal Deletion of CD4+ T Cells in Low-Dose Irradiated Mice: Role of T Cell Antigen Receptor and IL-7 Receptor Signals J. Immunol., December 15, 2006; 177(12): 8320 - 8330. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Martin, C. Becourt, B. Bienvenu, and B. Lucas Self-recognition is crucial for maintaining the peripheral CD4+ T-cell pool in a nonlymphopenic environment Blood, July 1, 2006; 108(1): 270 - 277. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-i. Sawa, D. Kamimura, G.-H. Jin, H. Morikawa, H. Kamon, M. Nishihara, K. Ishihara, M. Murakami, and T. Hirano Autoimmune arthritis associated with mutated interleukin (IL)-6 receptor gp130 is driven by STAT3/IL-7-dependent homeostatic proliferation of CD4+ T cells J. Exp. Med., June 12, 2006; 203(6): 1459 - 1470. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Shimoda, F. Mmanywa, S. K. Joshi, T. Li, K. Miyake, J. Pihkala, J. A. Abbas, and P. A. Koni Conditional Ablation of MHC-II Suggests an Indirect Role for MHC-II in Regulatory CD4 T Cell Maintenance. J. Immunol., June 1, 2006; 176(11): 6503 - 6511. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Hataye, J. J. Moon, A. Khoruts, C. Reilly, and M. K. Jenkins Naive and Memory CD4+ T Cell Survival Controlled by Clonal Abundance Science, April 7, 2006; 312(5770): 114 - 116. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Raimondi, I. Zanoni, S. Citterio, P. Ricciardi-Castagnoli, and F. Granucci Induction of Peripheral T Cell Tolerance by Antigen-Presenting B Cells. II. Chronic Antigen Presentation Overrules Antigen-Presenting B Cell Activation J. Immunol., April 1, 2006; 176(7): 4021 - 4028. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Jabbari and J. T. Harty Cutting Edge: Differential Self-Peptide/MHC Requirement for Maintaining CD8 T Cell Function versus Homeostatic Proliferation J. Immunol., October 15, 2005; 175(8): 4829 - 4833. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Pace, C. Pioli, and G. Doria IL-4 Modulation of CD4+CD25+ T Regulatory Cell-Mediated Suppression J. Immunol., June 15, 2005; 174(12): 7645 - 7653. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. J. Fry and C. L. Mackall The Many Faces of IL-7: From Lymphopoiesis to Peripheral T Cell Maintenance J. Immunol., June 1, 2005; 174(11): 6571 - 6576. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. J. Zhang, Q. Wang, J. Wei, G. Baimukanova, F. Buchholz, A. F. Stewart, X. Mao, and N. Killeen Selective Expression of the Cre Recombinase in Late-Stage Thymocytes Using the Distal Promoter of the Lck Gene J. Immunol., June 1, 2005; 174(11): 6725 - 6731. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Lombardi, D. Burzyn, J. Mundinano, P. Berguer, P. Bekinschtein, H. Costa, L. F. Castillo, A. Goldman, R. Meiss, I. Piazzon, et al. Cathepsin-L Influences the Expression of Extracellular Matrix in Lymphoid Organs and Plays a Role in the Regulation of Thymic Output and of Peripheral T Cell Number J. Immunol., June 1, 2005; 174(11): 7022 - 7032. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. A. Sullivan, L. M. Reed-Loisel, G. J. Kersh, and P. E. Jensen Homeostatic Proliferation of a Qa-1b-Restricted T Cell: A Distinction between the Ligands Required for Positive Selection and for Proliferation in Lymphopenic Hosts J. Immunol., November 15, 2004; 173(10): 6065 - 6071. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. A. Hagen, C. T. Moses, E. F. Drasler, K. M. Podetz-Pedersen, S. C. Jameson, and A. Khoruts A Role for CD28 in Lymphopenia-Induced Proliferation of CD4 T Cells J. Immunol., September 15, 2004; 173(6): 3909 - 3915. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. Wagner, M. Pierer, M. Wahle, F. Moritz, S. Kaltenhauser, and H. Hantzschel Ex Vivo Homeostatic Proliferation of CD4+ T Cells in Rheumatoid Arthritis Is Dysregulated and Driven by Membrane-Anchored TNF{alpha} J. Immunol., August 15, 2004; 173(4): 2825 - 2833. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. G. Thompson, B. J. O'Sullivan, H. Beamish, and R. Thomas T Cells Signaled by NF-{kappa}B- Dendritic Cells Are Sensitized Not Anergic to Subsequent Activation J. Immunol., August 1, 2004; 173(3): 1671 - 1680. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. M. Yankee, T. J. Yun, K. E. Draves, K. Ganesh, M. J. Bevan, K. Murali-Krishna, and E. A. Clark The Gads (GrpL) Adaptor Protein Regulates T Cell Homeostasis J. Immunol., August 1, 2004; 173(3): 1711 - 1720. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. L. Laurie, N. L. La Gruta, N. Koch, I. R. van Driel, and P. A. Gleeson Thymic Expression of a Gastritogenic Epitope Results in Positive Selection of Self-Reactive Pathogenic T Cells J. Immunol., May 15, 2004; 172(10): 5994 - 6002. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
C. T. Moses, K. M. Thorstenson, S. C. Jameson, and A. Khoruts Competition for self ligands restrains homeostatic proliferation of naive CD4 T cells PNAS, February 4, 2003; 100(3): 1185 - 1190. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Yasutomo Pathological lymphocyte activation by defective clearance of self-ligands in systemic lupus erythematosus Rheumatology, February 1, 2003; 42(2): 214 - 222. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Xi and G. J. Kersh Induction of the Early Growth Response Gene 1 Promoter by TCR Agonists and Partial Agonists: Ligand Potency Is Related to Sustained Phosphorylation of Extracellular Signal-Related Kinase Substrates J. Immunol., January 1, 2003; 170(1): 315 - 324. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-I. Rodriguez-Barbosa, Y. Zhao, G. Zhao, A. Ezquerra, and M. Sykes Murine CD4 T Cells Selected in a Highly Disparate Xenogeneic Porcine Thymus Graft Do Not Show Rapid Decay in the Absence of Selecting MHC in the Periphery J. Immunol., December 15, 2002; 169(12): 6697 - 6710. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. S. Cabatingan, M. R. Schmidt, R. Sen, and R. T. Woodland Naive B Lymphocytes Undergo Homeostatic Proliferation in Response to B Cell Deficit J. Immunol., December 15, 2002; 169(12): 6795 - 6805. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Jaleco, S. Kinet, J. Hassan, V. Dardalhon, L. Swainson, D. Reen, N. Taylor, and L. Al-Harthi IL-7 and CD4+ T-cell proliferation Blood, December 15, 2002; 100(13): 4676 - 4677. [Full Text] [PDF]
|
|
|
|
|
|
M. Gonzalez, S. A. Quezada, B. R. Blazar, A. Panoskaltsis-Mortari, A. Y. Rudensky, and R. J. Noelle The Balance Between Donor T Cell Anergy and Suppression Versus Lethal Graft-Versus-Host Disease Is Determined by Host Conditioning J. Immunol., November 15, 2002; 169(10): 5581 - 5589. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Adkins, Y. Bu, and P. Guevara Murine Neonatal CD4+ Lymph Node Cells Are Highly Deficient in the Development of Antigen-Specific Th1 Function in Adoptive Adult Hosts J. Immunol., November 1, 2002; 169(9): 4998 - 5004. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Seddon and R. Zamoyska TCR Signals Mediated by Src Family Kinases Are Essential for the Survival of Naive T Cells J. Immunol., September 15, 2002; 169(6): 2997 - 3005. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Dai and F. G. Lakkis Cutting Edge: Secondary Lymphoid Organs Are Essential for Maintaining the CD4, But Not CD8, Naive T Cell Pool J. Immunol., December 15, 2001; 167(12): 6711 - 6715. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Ploix, D. Lo, and M. J. Carson A Ligand for the Chemokine Receptor CCR7 Can Influence the Homeostatic Proliferation of CD4 T Cells and Progression of Autoimmunity J. Immunol., December 15, 2001; 167(12): 6724 - 6730. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. Wang, J. Strong, and N. Killeen Homeostatic Competition Among T Cells Revealed by Conditional Inactivation of the Mouse Cd4 Gene J. Exp. Med., December 10, 2001; 194(12): 1721 - 1730. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Smith, B. Seddon, M. A. Purbhoo, R. Zamoyska, A. G. Fisher, and M. Merkenschlager Sensory Adaptation in Naive Peripheral CD4 T Cells J. Exp. Med., October 29, 2001; 194(9): 1253 - 1262. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. Wang, L. Malherbe, D. Zhang, K. Zingler, N. Glaichenhaus, and N. Killeen CD4 Promotes Breadth in the TCR Repertoire J. Immunol., October 15, 2001; 167(8): 4311 - 4320. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Gudmundsdottir and L. A. Turka A Closer Look at Homeostatic Proliferation of CD4+ T Cells: Costimulatory Requirements and Role in Memory Formation J. Immunol., October 1, 2001; 167(7): 3699 - 3707. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Deshpande, M. Zheng, S. Lee, K. Banerjee, S. Gangappa, U. Kumaraguru, and B. T. Rouse Bystander Activation Involving T Lymphocytes in Herpetic Stromal Keratitis J. Immunol., September 1, 2001; 167(5): 2902 - 2910. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. C. Kieper, M. Prlic, C. S. Schmidt, M. F. Mescher, and S. C. Jameson IL-12 Enhances CD8 T Cell Homeostatic Expansion J. Immunol., May 1, 2001; 166(9): 5515 - 5521. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. Ge, V. P. Rao, B. K. Cho, H. N. Eisen, and J. Chen Dependence of lymphopenia-induced T cell proliferation on the abundance of peptide/ MHC epitopes and strength of their interaction with T cell receptors PNAS, February 13, 2001; 98(4): 1728 - 1733. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Strong, Q. Wang, and N. Killeen Impaired survival of T helper cells in the absence of CD4 PNAS, February 27, 2001; 98(5): 2566 - 2571. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Polic, D. Kunkel, A. Scheffold, and K. Rajewsky How alpha beta T cells deal with induced TCRalpha ablation PNAS, July 17, 2001; 98(15): 8744 - 8749. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. T. Tan, E. Dudl, E. LeRoy, R. Murray, J. Sprent, K. I. Weinberg, and C. D. Surh IL-7 is critical for homeostatic proliferation and survival of naive T cells PNAS, July 17, 2001; 98(15): 8732 - 8737. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
