Abstract |
To investigate if transporter associated with antigen processing (TAP)-1 is required for CD8(+) T cell-mediated control of Toxoplasma gondii in vivo, we compared the resistance of TAP-1(-/-), CD8(-/-), and wild-type (WT) mice to infection with the parasite. Unexpectedly, TAP-1(-/-) mice displayed greater susceptibility than CD8(-/-), beta(2)-microglobulin(-/-) (beta(2)m(-/-)), or WT mice to infection with an avirulent parasite strain. The decreased resistance of the TAP-1(-/-) mice correlated with a reduction in the frequency of activated (CD62L(low) CD44(hi)) and interferon (IFN)-gamma-producing CD4(+) T cells. Interestingly, infected TAP-1(-/-) mice also showed reduced numbers of IFN-gamma-producing natural killer (NK) cells relative to WT, CD8(-/-), or beta(2)m(-/-) mice, and after NK cell depletion both CD8(-/-) and WT mice succumbed to infection with the same kinetics as TAP-1(-/-) animals and displayed impaired CD4(+) T cell IFN-gamma responses. Moreover, adoptive transfer of NK cells obtained from IFN-gamma(+/+), but not IFN-gamma(-/-), animals restored the CD4(+) T cell response of infected TAP-1(-/-) mice to normal levels. These results reveal a role for TAP-1 in the induction of IFN-gamma-producing NK cells and demonstrate that NK cell licensing can influence host resistance to infection through its effect on cytokine production in addition to its role in cytotoxicity.
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Authors | Romina S Goldszmid, Andre Bafica, Dragana Jankovic, Carl G Feng, Pat Caspar, Robin Winkler-Pickett, Giorgio Trinchieri, Alan Sher |
Journal | The Journal of experimental medicine
(J Exp Med)
Vol. 204
Issue 11
Pg. 2591-602
(Oct 29 2007)
ISSN: 1540-9538 [Electronic] United States |
PMID | 17923502
(Publication Type: Journal Article, Research Support, N.I.H., Intramural)
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Chemical References |
- ATP Binding Cassette Transporter, Subfamily B, Member 2
- ATP-Binding Cassette Transporters
- Tap1 protein, mouse
- beta 2-Microglobulin
- Interferon-gamma
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Topics |
- ATP Binding Cassette Transporter, Subfamily B, Member 2
- ATP-Binding Cassette Transporters
(genetics, immunology)
- Animals
- CD8-Positive T-Lymphocytes
(immunology)
- Dendritic Cells
(immunology, parasitology)
- Genetic Predisposition to Disease
- Interferon-gamma
(immunology)
- Killer Cells, Natural
(immunology)
- Mice
- Mice, Knockout
- Toxoplasma
(growth & development, immunology)
- Toxoplasmosis
(immunology)
- beta 2-Microglobulin
(deficiency, immunology)
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