Viral inoculum dose impacts memory T-cell inflation.

Area of Science:

• Immunology
• Virology
• Cellular Biology

Background:

• Memory T-cell inflation, a hallmark of persistent viral infections like cytomegalovirus (CMV), involves accumulating effector-memory T cells.
• The mechanisms controlling the magnitude and phenotype of this T-cell response remain incompletely understood.
• Variability in human CMV-specific T-cell responses suggests influencing factors are at play.

Purpose of the Study:

• To investigate the role of the initial viral infectious dose in shaping memory T-cell inflation.
• To understand how inoculum size affects the accumulation, phenotype, and function of CMV-specific memory T cells.
• To correlate viral load and T-cell dynamics with the initial infectious dose.

Main Methods:

• Utilized a mouse cytomegalovirus (CMV) model with varying inoculum sizes to study T-cell responses.
• Quantified CMV-specific memory T-cell formation, viral reservoirs in nonhematopoietic cells, and T-cell proliferation.
• Analyzed T-cell phenotype using cell-surface markers (CD27, CD62L, CD127, KLRG1) and assessed secondary expansion potential.

Main Results:

• Low-dose CMV inoculum significantly hampered the accumulation of inflationary memory T cells.
• Reduced viral reservoirs in nonhematopoietic cells and diminished antigen-driven T-cell proliferation were observed with lower doses.
• Lower initial viral doses shifted T cells from an effector-memory to a central-memory phenotype (CD27high, CD62L+, CD127+, KLRG1-) with enhanced secondary expansion.

Conclusions:

• The initial viral inoculum size is a critical determinant of memory T-cell inflation magnitude and phenotype.
• Lower infectious doses lead to less inflation, altered T-cell phenotypes, and reduced viral persistence.
• These findings provide a mechanistic explanation for the observed variations in human CMV-specific T-cell immunity.