CD27 is required for protective lytic EBV antigen-specific CD8+ T-cell expansion

Area of Science:

• Immunology
• Virology
• Molecular Biology

Background:

• Primary immunodeficiencies affecting the CD27-CD70 costimulatory pathway are linked to severe Epstein-Barr virus (EBV) pathologies.
• Uncontrolled EBV infection can lead to significant morbidity and mortality, particularly in immunocompromised individuals.

Purpose of the Study:

• To investigate the role of the CD27-CD70 interaction in controlling EBV infection.
• To determine how CD27 signaling influences CD8+ T-cell responses against EBV.

Main Methods:

• Utilized a humanized mouse model with reconstituted immune system components.
• Administered CD27+ cell depletion or CD27-CD70 blocking antibodies.
• Assessed EBV infection control, CD8+ T-cell expansion, proliferation, and cytotoxic activity against EBV-infected cells.

Main Results:

• Depletion of CD27+ cells or blocking CD27-CD70 interaction led to uncontrolled EBV infection in humanized mice.
• While overall CD8+ T-cell numbers remained unchanged, specific EBV-specific CD8+ T-cell responses, such as those targeting BMLF1, showed inhibited proliferation and killing capacity.
• CD27 signaling is essential for a subset of protective CD8+ T-cell responses, not all.

Conclusions:

• The CD27-CD70 pathway is critical for effective immune surveillance against EBV.
• CD27 plays a vital role in orchestrating specific CD8+ T-cell effector functions required to control EBV, thereby preventing associated pathologies.