Cytomegalovirus mediates expansion of IL-15-responsive innate-memory cells with SIV killing function

Area of Science:

• Immunology
• Virology
• Vaccinology

Background:

• Interindividual immune variability is influenced by environmental factors, notably chronic infections like cytomegalovirus (CMV).
• Rhesus CMV (RhCMV) is a significant factor in macaques, impacting immune cell populations.

Purpose of the Study:

• To investigate the effects of RhCMV infection on the composition and function of the immune system in young macaques.
• To evaluate immune changes following administration of RhCMV-vectored SIV vaccines.

Main Methods:

• Analysis of immune cell populations (antigen presenting cells, T cells, NK cells) post-RhCMV infection.
• In vitro and in vivo studies using IL-15 to assess T cell differentiation.
• Assessment of cytotoxicity and IFN-γ production of expanded CD8+ T cells.
• Evaluation of SIV inhibition by CD8+ T cells post-vaccination.

Main Results:

• RhCMV infection induced significant changes in immune cells, including the expansion of innate-memory CD8+ T cells expressing NKG2A/C and CD122.
• These expanded CD8+ T cells demonstrated cytotoxicity and IFN-γ production.
• RhCMV-vectored SIV vaccines also expanded NKG2A/C+CD8+ T cells capable of inhibiting SIV replication ex vivo.
• Host IL-15 production was identified as a key driver for the differentiation of these innate-like CD8+ T cells.

Conclusions:

• CMV infection and CMV-vectored vaccination promote the expansion of functional innate-like CD8+ T cells.
• Host IL-15 plays a crucial role in driving the differentiation of these expanded CD8+ T cells.
• This suggests that innate-memory T cell expansion could be a target for other vaccine platforms, potentially by incorporating IL-15 expression.