Functional consequences of memory inflation after solid organ transplantation

Lauren E. Higdon, Steven Schaffert, Rachel H. Cohen, Maria E. Montez-Rath, Marc Lucia, Naresha Saligrama, Kenneth B. Margulies, Olivia M. Martinez, Jane C. Tan, Mark M. Davis, Purvesh Khatri, Jonathan S. Maltzman

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

CMV is a major infectious complication following solid organ transplantation. Reactivation of CMV leads to memory inflation, a process in which CD8 T cells expand over time. Memory inflation is associated with specific changes in T cell function, including increased oligoclonality, decreased cytokine production, and terminal differentiation. To address whether memory inflation during the first year after transplantation in human subjects alters T cell differentiation and function, we employed single-cell-matched TCRab and targeted gene expression sequencing. Expanded T cell clones exhibited a terminally differentiated, immunosenescent, and polyfunctional phenotype whereas rare clones were less differentiated. Clonal expansion occurring between pre- and 3 mo posttransplant was accompanied by enhancement of polyfunctionality. In contrast, polyfunctionality and differentiation state were largely maintained between 3 and 12 mo posttransplant. Highly expanded clones had a higher degree of polyfunctionality than rare clones. Thus, CMV-responsive CD8 T cells differentiated during the pre- to posttransplant period then maintained their differentiation state and functional capacity despite posttransplant clonal expansion.

Original languageEnglish
Pages (from-to)2086-2095
Number of pages10
JournalJournal of Immunology
Volume207
Issue number8
DOIs
StatePublished - Oct 15 2021

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