Functional CD8 T cell memory responding to persistent latent infection is maintained for life.

Area of Science:

• Immunology
• Gerontology
• Virology

Background:

• Aging impairs naive T cell responses, but memory T cell function over time remains unclear.
• Persistent infections require lifelong T cell memory for control.
• Herpes Simplex Virus-1 (HSV-1) infection causes CD8 T cell memory inflation.

Purpose of the Study:

• To investigate the maintenance and function of virus-specific CD8 T cell memory from adulthood into old age.
• To determine if age-related changes affect the long-term functionality of memory T cells controlling persistent infections.

Main Methods:

• Comparison of memory T cell numbers, ex vivo antigen-specific IFN-γ production, and in vivo recall responses in adult vs. old mice infected with HSV-1.
• Phenotypic analysis of memory CD8 T cells, including KLRG1 expression.
• Assessment of KLRG1(+) memory CD8 T cell function in response to homeostatic signals in vitro and in vivo.

Main Results:

• No significant age-related differences in memory T cell numbers or HSV-1 recall responses (proliferation, IFN-γ production, cytolysis).
• A shift in phenotype from effector memory in adults to central memory-like in old mice, with fewer KLRG1(+) cells in older mice.
• Adult and old KLRG1(+) memory CD8 T cells showed identical IFN-γ production but limited proliferation to viral challenge.
• KLRG1(+) cells, irrespective of age, maintained proliferative and survival capacity in response to homeostatic signals.

Conclusions:

• Functional effector memory CD8 T cells, including KLRG1(+) cells, are maintained throughout life.
• These memory T cells remain capable of controlling persistent infections like HSV-1 even in old age.
• Lifelong T cell memory function is robust, despite potential dysregulation from chronic stimulation.