Recent thymic emigrants are preferentially recruited into the memory pool during persistent infection

Area of Science:

• Immunology
• Virology
• T cell biology

Background:

• Cytomegalovirus (CMV) infection induces 'memory inflation,' a sustained accumulation of memory CD8+ T cells in peripheral tissues during latency.
• The precise mechanisms governing the generation and maintenance of this inflating CD8+ T cell pool remain incompletely understood.

Purpose of the Study:

• To investigate the dynamics of CD8+ T cell recruitment into the memory pool during persistent Cytomegalovirus (CMV) infection.
• To differentiate the contributions of newly generated versus mature T cells to the memory pool.

Main Methods:

• Utilized murine cytomegalovirus (MCMV) as a model system for persistent infection.
• Employed fate-mapping mice to track the origin and differentiation of CD8+ T cells.
• Analyzed phenotypic differences between recent thymic emigrants (RTEs) and mature T cells.

Main Results:

• Neonatal CMV exposure results in the expansion and long-term maintenance of recent thymic emigrants (RTEs) within the memory CD8+ T cell compartment.
• Mature CD8+ T cells generated during the latent phase contribute minimally to the memory pool.
• RTEs present during initial infection differentiate into effector memory cells, while later-produced T cells favor central memory phenotypes.
• Preferential recruitment of RTEs into the effector memory pool is observed in both neonatal and adult CMV infection.

Conclusions:

• Persistent CMV infection promotes the expansion of the RTE population.
• The timing of CMV infection critically influences which cohort of RTEs (neonatal or adult) becomes 'locked in' to the long-lived memory pool.
• These findings elucidate key aspects of CD8+ T cell memory formation during chronic viral infections.