Reduced Bordetella pertussis-specific CD4⁺ T-Cell Responses at Older Age

Area of Science:

• Immunology
• Infectious Diseases
• Bacteriology

Background:

• Pertussis (whooping cough) remains a significant public health concern, with endemic circulation and epidemic outbreaks despite high vaccination rates.
• While pertussis vaccines and infection provide immunity, protection is not lifelong, and the disease burden in older adults is underestimated.
• The impact of aging on humoral immunity to Bordetella pertussis (Bp) is known, but age-related changes in CD4+ T-cell responses are poorly understood.

Purpose of the Study:

• To investigate whether increasing age affects the responsiveness of Bordetella pertussis (Bp)-specific CD4+ T-cells in the memory pool after symptomatic pertussis infection.
• To compare cytokine production, proliferative capacity, and phenotypic profiles of Bp-specific CD4+ T-cells in pediatric and adult pertussis cases at different convalescent time points.

Main Methods:

• Comparison of cytokine responses (including IFNγ) and CD4+ T-cell proliferation in pediatric and adult pertussis survivors at early and late convalescent stages.
• Phenotypic analysis of Bp-specific CD4+ T-cells to assess activation and co-inhibitory marker expression.

Main Results:

• Older adults exhibited significantly lower Th cytokine responses, including IFNγ, at both early and late time points post-pertussis diagnosis.
• Frequencies of Bp-specific proliferated CD4+ T-cells were reduced in older adults, without differences in replication.
• Phenotyping indicated reduced expression of activation markers on Bp-specific CD4+ T-cells in older adults, rather than increased co-inhibitory marker expression.

Conclusions:

• The magnitude and functionality of the Bp-specific memory CD4+ T-cell pool decline with increasing age.
• Reduced CD4+ T-cell responsiveness to Bordetella pertussis in older adults may contribute to the increased burden of pertussis in this population.
• These findings highlight the importance of understanding immunosenescence in the context of pertussis and may inform future vaccination strategies.