Rationale: Individuals with advanced age are at a progressively increasing risk of acquiring lower respiratory tract infections. Besides calendar age, the degree of frailty also associates with increased susceptibility to pneumonia requiring hospitalization. How alterations in the mucosal immune system with advanced age predispose to infections remains unclear as access to relevant tissue samples is limited. With minimally-invasive nasal sampling methods, it was recently observed that in vital older adults, both CD4+ T cells and CD8+ T cells are selectively lost from the nasal mucosa. However, the exact phenotype, underlying mechanisms, key molecules and consequences of this have not yet been investigated. Objective: Elucidate the mechanisms underlying the loss of nasal T cells and characterize in depth the differences of T cells in young and older adults and associate this loss with susceptibility to infections. Study design: Prospective cohort study Study population: Participants will be recruited from 3 groups: * healthy young adults (18-30 years, n=50) * vital older adults (\>65 years, n=60) * frail elderly (\>65 years, n=60). This group includes individuals without a history of recurrent respiratory infections or with \>2 self-reported episodes of respiratory infection in the past year. Main study parameters/endpoints: Frequency of nasal CD8+ T cells in young adults and frail older adults. Secondary study parameters/endpoints: * Phenotype (subsets, activation status), functionality, transcriptomic state, clonality and frequency of nasal and blood T cell populations * Stability of T cells and other immune parameters, as described for main study parameter, during a second sample after 3 months. * Analysis of other immune populations as for main study parameter * Concentration of nasal and systemic factors (e.g. cytokines and metabolites) and their association with T cells and other immune populations * Respiratory tract microbiota profiles and presence of asymptomatic viral infections and their association with T cells and other immune parameters * Chronological and biological age, sex, and other immunologically relevant parameters with T cell populations and other immune parameters * Alteration of T cell phenotype, during and following respiratory tract infections. Levels of antigen-specific T cells and other immune parameters in nose and blood post infection.
Study Type
OBSERVATIONAL
Enrollment
125
Leiden University Medical Center
Leiden, South Holland, Netherlands
Frequency of nasal CD8+ T cells in young adults and frail older adults.
CD8 T cells relative to nasal epithelial cells (ratio)
Time frame: baseline sample or month 3 sample
Phenotype of nasal and blood T cell populations in young adults, healthy older adults and frail older adults that suffer from recurrent respiratory tract infections or not.
percentage of T cells and T cell subsets
Time frame: baseline sample or month 3 sample
Functionality of nasal and blood T cell populations in young adults, healthy older adults and frail older adults that suffer from recurrent respiratory tract infections or not.
percentage of T cells responding to in vitro stimulations
Time frame: baseline sample or month 3 sample
Transcriptomic cluster composition of nasal and blood T cell populations in young adults, healthy older adults and frail older adults that suffer from recurrent respiratory tract infections or not, as frequency of T cell subsets.
T cell clusters based on gene expression patterns
Time frame: baseline sample or month 3 sample
Clonality of nasal and blood T cell populations in young adults, healthy older adults and frail older adults that suffer from recurrent respiratory tract infections or not.
Number and proportion of TCR clones
Time frame: baseline sample or month 3 sample
Stability of nasal T cells, as described for main study parameter, during a second sample after 3 months.
CD8 T cells relative to nasal epithelial cells (ratio)
Time frame: baseline sample versus month 3 sample
Stability of nasal immune populations, during a second sample after 3 months.
immune cell populations relative to nasal epithelial cells (ratio)
Time frame: baseline sample versus month 3 sample
Comparison of nasal immune cell populations between young adults, vital and frail elderly
ratio to epithelial cells
Time frame: baseline sample or month 3 sample
Comparison of peripheral immune cell populations between young adults, vital and frail elderly
percentage of total CD45+ cells
Time frame: baseline sample or month 3 sample
Concentration of nasal and systemic cytokines
concentrations
Time frame: baseline sample or month 3 sample
Concentration of nasal and systemic metabolitesother immune populations
concentrations
Time frame: baseline sample or month 3 sample
Respiratory tract microbiota profiles and their association with T cells and other immune parameters
microbiota abundance (total sum scaling)
Time frame: baseline sample or month 3 sample
Presence of asymptomatic viral infections and their association with T cells and other immune parameters
viral of loads (Ct)
Time frame: baseline sample or month 3 sample
Effect of sex on aging effects of nasal immune populations
ratio to nasal epithelial cells
Time frame: baseline sample or month 3 sample
Effect of sex on aging effects of blood immune populations
percentage of CD45+ cells
Time frame: baseline sample or month 3 sample
Frequencies of antigen-specific T cells in nose post infection.
antigen-specific T cells as percentage of T cells
Time frame: symptom onset and 1, 3 and 5 months later
Frequencies of antigen-specific T cells in blood post infection.
antigen-specific T cells as percentage of T cells
Time frame: symptom onset and 1, 3 and 5 months later
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