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The Inhibitory Receptor NKG2A Sustains Virus-Specific CD8⁺ T Cells in Response to a Lethal Poxvirus Infection
Aaron S Rapaport1, Jill Schriewer2, Susan Gilfillan1
1Department of Pathology and Immunology, Washington University School of Medicine, 660 S. Euclid, St. Louis, MO 63110, USA.
Immunity
|December 19, 2015
Summary
NKG2A, an inhibitory receptor, is crucial for CD8(+) T cell responses against ectromelia virus (ECTV). It optimizes T cell function during acute viral infections, preventing exhaustion and promoting resistance.
Area of Science:
- Immunology
- Virology
- Cell Biology
Background:
- CD8(+) T cells and NK cells are vital for antiviral immunity, secreting interferon-gamma and eliminating infected cells.
- Inhibitory receptors, such as NKG2A (encoded by Klrc1) complexed with CD94, regulate T cell and NK cell responses.
- The in vivo role of NKG2A in antiviral immunity has been debated, with conflicting previous findings.
Purpose of the Study:
- To elucidate the in vivo function of the inhibitory receptor NKG2A in antiviral responses.
- To investigate the specific role of NKG2A in CD8(+) T cell-mediated immunity against poxvirus infections.
Main Methods:
- Generation and analysis of Klrc1(-/-) knockout mice.
- Assessment of anti-viral immune responses following ectromelia virus (ECTV) infection in wild-type and Klrc1(-/-) mice.
Main Results:
- NKG2A is essential for host resistance to ectromelia virus (ECTV) infection.
- NKG2A functions within ECTV-specific CD8(+) T cells to limit excessive activation and apoptosis.
- Absence of NKG2A preserves the CD8(+) T cell response during acute ECTV infection.
Conclusions:
- Contrary to expectations for chronic infections, NKG2A optimizes CD8(+) T cell responses during acute poxvirus infections.
- NKG2A plays a critical, context-dependent role in regulating T cell-mediated antiviral immunity.
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