Functional Consequences of Memory Inflation after Solid Organ Transplantation.

Area of Science:

• Immunology
• Transplantation Medicine
• Virology

Background:

• Cytomegalovirus (CMV) is a significant infectious complication after solid organ transplantation.
• CMV reactivation triggers CD8 T cell memory inflation, characterized by T cell expansion and functional alterations.

Purpose of the Study:

• To investigate how CMV-induced memory inflation affects T cell differentiation and function in the first year post-transplant.
• To analyze changes in T cell phenotype, differentiation, and function during CMV-associated memory inflation.

Main Methods:

• Utilized single-cell-matched TCRαβ sequencing and targeted gene expression analysis.
• Compared T cell populations from pre-transplant to 3 and 12 months post-transplant.

Main Results:

• Expanded T cell clones showed a terminally differentiated, immunosenescent, and polyfunctional phenotype.
• Polyfunctionality increased between pre- and 3 months post-transplant, then remained stable.
• Highly expanded clones exhibited greater polyfunctionality than rare clones.

Conclusions:

• CMV-responsive CD8 T cells differentiate early post-transplant and maintain their state and function.
• Despite clonal expansion, T cells retain functional capacity throughout the first year.