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Science 17 November 2000:
Vol. 290. no. 5495, pp. 1354 - 1357
DOI: 10.1126/science.290.5495.1354
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Reports

Regulation of Antigen-Specific CD8+ T Cell Homeostasis by Perforin and Interferon-gamma

Vladimir P. Badovinac,1 Amy R. Tvinnereim,1 John T. Harty12*

T cell memory depends on factors that regulate expansion and death of these cells after antigenic stimulation. Mice deficient in perforin and interferon-gamma (IFN-gamma ) exhibited increased expansion, altered immunodominance, and decreased death of antigen-specific CD8+ T cells after infection with an attenuated strain of Listeria monocytogenes, which was cleared from these mice. Expansion of CD8+ T cells was controlled by perforin, whereas IFN-gamma regulated immunodominance and the death phase. Thus, perforin and IFN-gamma regulate distinct elements of CD8+ T cell homeostasis independently of their role as antimicrobial effector molecules.

1 Department of Microbiology and
2 Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, IA 52242, USA.
*   To whom correspondence should be addressed. E-mail: john-harty{at}uiowa.edu

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Perforin-Mediated Effector Function Within the Central Nervous System Requires IFN-{gamma}-Mediated MHC Up-Regulation.
C. C. Bergmann, B. Parra, D. R. Hinton, R. Chandran, M. Morrison, and S. A. Stohlman (2003)
J. Immunol. 170, 3204-3213
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Activation of Natural Killer T Cells by {alpha}-Galactosylceramide Impairs DNA Vaccine-Induced Protective Immunity against Trypanosoma cruzi.
Y. Miyahira, M. Katae, K. Takeda, H. Yagita, K. Okumura, S. Kobayashi, T. Takeuchi, T. Kamiyama, Y. Fukuchi, and T. Aoki (2003)
Infect. Immun. 71, 1234-1241
   Abstract »    Full Text »    PDF »
Cutting Edge: Perforin Down-Regulates CD4 and CD8 T Cell-Mediated Immune Responses to a Transplanted Organ.
A. Bose, Y. Inoue, K. E. Kokko, and F. G. Lakkis (2003)
J. Immunol. 170, 1611-1614
   Abstract »    Full Text »    PDF »
TNF Plays an Essential Role in Tumor Regression after Adoptive Transfer of Perforin/IFN-{gamma} Double Knockout Effector T Cells.
C. H. Poehlein, H.-M. Hu, J. Yamada, I. Assmann, W. G. Alvord, W. J. Urba, and B. A. Fox (2003)
J. Immunol. 170, 2004-2013
   Abstract »    Full Text »    PDF »
Perforin-Dependent Brain-Infiltrating Cytotoxic CD8+ T Lymphocytes Mediate Experimental Cerebral Malaria Pathogenesis.
J. Nitcheu, O. Bonduelle, C. Combadiere, M. Tefit, D. Seilhean, D. Mazier, and B. Combadiere (2003)
J. Immunol. 170, 2221-2228
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Preferential Escape of Subdominant CD8+ T Cells During Negative Selection Results in an Altered Antiviral T Cell Hierarchy.
M. K. Slifka, J. N. Blattman, D. J. D. Sourdive, F. Liu, D. L. Huffman, T. Wolfe, A. Hughes, M. B. A. Oldstone, R. Ahmed, and M. G. von Herrath (2003)
J. Immunol. 170, 1231-1239
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Blockade of Programmed Death-1 Ligands on Dendritic Cells Enhances T Cell Activation and Cytokine Production.
J. A. Brown, D. M. Dorfman, F.-R. Ma, E. L. Sullivan, O. Munoz, C. R. Wood, E. A. Greenfield, and G. J. Freeman (2003)
J. Immunol. 170, 1257-1266
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Complement Component 3 Is Required for Optimal Expansion of CD8 T Cells During a Systemic Viral Infection.
M. Suresh, H. Molina, M. S. Salvato, D. Mastellos, J. D. Lambris, and M. Sandor (2003)
J. Immunol. 170, 788-794
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Ablation of CD8 and CD4 T Cell Responses by High Viral Loads.
M. J. Fuller and A. J. Zajac (2003)
J. Immunol. 170, 477-486
   Abstract »    Full Text »    PDF »
Quantitation of CD8+ T Cell Expansion, Memory, and Protective Immunity After Immunization with Peptide-Coated Dendritic Cells.
S. E. Hamilton and J. T. Harty (2002)
J. Immunol. 169, 4936-4944
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Perforin-Mediated CTL Cytolysis Counteracts Direct Cell-Cell Spread of Listeria monocytogenes.
L. R. San Mateo, M. M. Chua, S. R. Weiss, and H. Shen (2002)
J. Immunol. 169, 5202-5208
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Single-chain antigen recognition receptors that costimulate potent rejection of established experimental tumors.
N. M. Haynes, J. A. Trapani, M. W. L. Teng, J. T. Jackson, L. Cerruti, S. M. Jane, M. H. Kershaw, M. J. Smyth, and P. K. Darcy (2002)
Blood 100, 3155-3163
   Abstract »    Full Text »    PDF »
Interferon {gamma} Is Required for Activation-induced Death of T Lymphocytes.
Y. Refaeli, L. Van Parijs, S. I. Alexander, and A. K. Abbas (2002)
J. Exp. Med. 196, 999-1005
   Abstract »    Full Text »    PDF »


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