Abstract
SARS-CoV-2 infection and vaccination generates enormous host-response heterogeneity and an age-dependent loss of immune-response quality. How the pre-exposure T cell repertoire contributes to this heterogeneity is poorly understood. We combined analysis of SARS-CoV-2-specific CD4 + T cells pre- and post-vaccination with longitudinal T cell receptor tracking. We identified strong pre-exposure T cell variability that correlated with subsequent immune-response quality and age. High-quality responses, defined by strong expansion of high-avidity spike-specific T cells, high interleukin-21 production, and specific immunoglobulin G, depended on an intact naive repertoire and exclusion of pre-existing memory T cells. In the elderly, T cell expansion from both compartments was severely compromised. Our results reveal that an intrinsic defect of the CD4 + T cell repertoire causes the age-dependent decline of immune-response quality against SARS-CoV-2 and highlight the need for alternative strategies to induce high-quality T cell responses against newly arising pathogens in the elderly.
Keywords: CD154; CD40L; COVID-19; SARS-CoV-2; TCR tracking; antigen-reactive T cell enrichment; antigen-specific CD4+ T cells; vaccination.
【저자키워드】 COVID-19, SARS-CoV-2, CD40L, vaccination., antigen-specific CD4+ T cells, antigen-reactive T cell enrichment, TCR tracking, CD154, 【초록키워드】 vaccination, T cells, Infection, CD4, heterogeneity, T cell, pathogen, Immunoglobulin, memory T cells, age, TCR, T cell receptor, T cell response, Analysis, Variability, CD4+, host-response, exclusion, responses, highlight, intrinsic, defined, subsequent, generate, arising, contribute, correlated, induce, cause, 【제목키워드】 immune response, vaccination, T cell, determine,