| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Department Microbiology and Immunology, University of Melbourne, Parkville, Australia;
Walter and Eliza Hall Institute, Melbourne, Australia; and
Cancer Immunology Program, Peter MacCallum Cancer Center, Melbourne, Australia
Activation of NKT cells using the glycolipid 
-galactosylceramide (-GalCer) has availed many investigations into their immunoregulatory and therapeutic potential. However, it remains unclear how they respond to stimulation in vivo, which costimulatory pathways are important, and what factors (e.g., Ag availability and activation-induced cell death) limit their response. We have explored these questions in the context of an in vivo model of NKT cell dynamics spanning activation, population expansion, and subsequent contraction. Neither the B7/CD28 nor the CD40/CD40L costimulatory pathway was necessary for cytokine production by activated NKT cells, either early (2 h) or late (3 days) after initial stimulation, but both pathways were necessary for normal proliferative expansion of NKT cells in vivo. The proapoptotic Bcl-2 family member Bim was necessary for normal contraction of the NKT cell population between days 3–9 after stimulation, suggesting that the pool size is regulated by apoptotic death, similar to that of conventional T cells. Ag availability was not the limiting factor for NKT cell expansion in vivo, and a second -GalCer injection induced a very blunted response, whereby cytokine production was reduced and further expansion did not occur. This appeared to be a form of anergy that was intrinsic to NKT cells and was not associated with inhibitory NK receptor signaling. Furthermore, NKT cells from mice prechallenged with -GalCer in vivo showed little cytokine production and reduced proliferation in vitro. In summary, this study significantly enhances our understanding of how NKT cells respond to primary and secondary antigenic challenge in vivo.
This article has been cited by other articles:
|
|
 |
|
  J. Wang, L. Cheng, Z. Wondimu, M. Swain, P. Santamaria, and Y. Yang Cutting Edge: CD28 Engagement Releases Antigen-Activated Invariant NKT Cells from the Inhibitory Effects of PD-1 J. Immunol., June 1, 2009; 182(11): 6644 - 6647. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Guillonneau, J. D. Mintern, F.-X. Hubert, A. C. Hurt, G. S. Besra, S. Porcelli, I. G. Barr, P. C. Doherty, D. I. Godfrey, and S. J. Turner Combined NKT cell activation and influenza virus vaccination boosts memory CTL generation and protective immunity PNAS, March 3, 2009; 106(9): 3330 - 3335. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. V. Parekh, S. Lalani, S. Kim, R. Halder, M. Azuma, H. Yagita, V. Kumar, L. Wu, and L. Van Kaer PD-1/PD-L Blockade Prevents Anergy Induction and Enhances the Anti-Tumor Activities of Glycolipid-Activated Invariant NKT Cells J. Immunol., March 1, 2009; 182(5): 2816 - 2826. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Kawamura, K. Takeda, H. Kaneda, H. Matsumoto, Y. Hayakawa, D. H. Raulet, Y. Ikarashi, M. Kronenberg, H. Yagita, K. Kinoshita, et al. NKG2A Inhibits Invariant NKT Cell Activation in Hepatic Injury J. Immunol., January 1, 2009; 182(1): 250 - 258. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Chiba, C. C. Dascher, G. S. Besra, and M. B. Brenner Rapid NKT Cell Responses Are Self-Terminating during the Course of Microbial Infection J. Immunol., August 15, 2008; 181(4): 2292 - 2302. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Coquet, S. Chakravarti, K. Kyparissoudis, F. W. McNab, L. A. Pitt, B. S. McKenzie, S. P. Berzins, M. J. Smyth, and D. I. Godfrey Diverse cytokine production by NKT cell subsets and identification of an IL-17-producing CD4-NK1.1- NKT cell population PNAS, August 12, 2008; 105(32): 11287 - 11292. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Biburger and G. Tiegs Activation-induced NKT cell hyporesponsiveness protects from {alpha}-galactosylceramide hepatitis and is independent of active transregulatory factors J. Leukoc. Biol., July 1, 2008; 84(1): 264 - 279. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Akbari, P. Stock, E. H. Meyer, G. J. Freeman, A. H. Sharpe, D. T. Umetsu, and R. H. DeKruyff ICOS/ICOSL Interaction Is Required for CD4+ Invariant NKT Cell Function and Homeostatic Survival J. Immunol., April 15, 2008; 180(8): 5448 - 5456. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Chung, R. Nurieva, E. Esashi, Y.-H. Wang, D. Zhou, L. Gapin, and C. Dong A Critical Role of Costimulation during Intrathymic Development of Invariant NK T Cells J. Immunol., February 15, 2008; 180(4): 2276 - 2283. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. W. McNab, D. G. Pellicci, K. Field, G. Besra, M. J. Smyth, D. I. Godfrey, and S. P. Berzins Peripheral NK1.1 NKT Cells Are Mature and Functionally Distinct from Their Thymic Counterparts J. Immunol., November 15, 2007; 179(10): 6630 - 6637. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Coppieters, K. Van Beneden, P. Jacques, P. Dewint, A. Vervloet, B. Vander Cruyssen, S. Van Calenbergh, G. Chen, R. W. Franck, G. Verbruggen, et al. A Single Early Activation of Invariant NK T Cells Confers Long-Term Protection against Collagen-Induced Arthritis in a Ligand-Specific Manner J. Immunol., August 15, 2007; 179(4): 2300 - 2309. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Galli, P. Pittoni, E. Tonti, C. Malzone, Y. Uematsu, M. Tortoli, D. Maione, G. Volpini, O. Finco, S. Nuti, et al. Invariant NKT cells sustain specific B cell responses and memory PNAS, March 6, 2007; 104(10): 3984 - 3989. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Cheng, A. Ueno, S. Cho, J. S. Im, S. Golby, S. Hou, S. A. Porcelli, and Y. Yang Efficient Activation of V{alpha}14 Invariant NKT Cells by Foreign Lipid Antigen Is Associated with Concurrent Dendritic Cell-Specific Self Recognition J. Immunol., March 1, 2007; 178(5): 2755 - 2762. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Coquet, K. Kyparissoudis, D. G. Pellicci, G. Besra, S. P. Berzins, M. J. Smyth, and D. I. Godfrey IL-21 Is Produced by NKT Cells and Modulates NKT Cell Activation and Cytokine Production J. Immunol., March 1, 2007; 178(5): 2827 - 2834. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Shimizu, A. Goto, M. Fukui, M. Taniguchi, and S.-i. Fujii Tumor Cells Loaded with {alpha}-Galactosylceramide Induce Innate NKT and NK Cell-Dependent Resistance to Tumor Implantation in Mice J. Immunol., March 1, 2007; 178(5): 2853 - 2861. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Forestier, T. Takaki, A. Molano, J. S. Im, I. Baine, E. S. Jerud, P. Illarionov, R. Ndonye, A. R. Howell, P. Santamaria, et al. Improved Outcomes in NOD Mice Treated with a Novel Th2 Cytokine-Biasing NKT Cell Activator J. Immunol., February 1, 2007; 178(3): 1415 - 1425. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. J. Zullo, K. Benlagha, A. Bendelac, and E. J. Taparowsky Sensitivity of NK1.1-Negative NKT Cells to Transgenic BATF Defines a Role for Activator Protein-1 in the Expansion and Maturation of Immature NKT Cells in the Thymus J. Immunol., January 1, 2007; 178(1): 58 - 66. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Ly, Q.-S. Mi, S. Hussain, and T. L. Delovitch Protection from Type 1 Diabetes by Invariant NK T Cells Requires the Activity of CD4+CD25+ Regulatory T Cells J. Immunol., September 15, 2006; 177(6): 3695 - 3704. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
