TAP-1 indirectly regulates CD4+ T cell priming in Toxoplasma gondii infection by controlling NK cell IFN-gamma production.

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.

• 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)

Chemical References

• ATP Binding Cassette Transporter, Subfamily B, Member 2
• ATP-Binding Cassette Transporters
• Tap1 protein, mouse
• beta 2-Microglobulin
• Interferon-gamma

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)