TINO: Identifying the Underlying Mechanisms and Consequences of the Loss of Nasal T Cells in Vital and Frail Older Individuals

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.