T cell response to influenza vaccination remains intact in adults with congenital heart disease who underwent early thymectomy

ABSTRACT

Introduction: Thymectomy is routine during surgery for congenital heart defects to access to the heart. T cells developed in the thymus play a key role in immunity. Individuals with thymectomy in infancy have altered T cell populations suggesting early immunosenescence. Hypothesis: Adults with Congenital Heart Disease (ACHD) who underwent thymectomy in the first year of life have an altered response to influenza vaccination due to T cell immunosenescence. Methods: We recruited ACHD with early thymectomy ≤ 1 year of age (ACHD-ET;n = 12), ACHD and no thymectomy (ACHD-NT;n = 8), and healthy controls (HC;n = 14). Peripheral blood was collected prior to influenza vaccine and 4 weeks following administration. Flow cytometry of T cell subsets and intracellular cytokine staining of CD4 T cells was done following in vitro stimulation with influenza viral antigen. Results: Subject's mean age was 34 ± 10.6 years with no difference between the groups. At baseline, the median (IQR) frequency of naïve CD4 T cells was 24.7% (15.9) in ACHD-ET vs. 43.6% (16.9) in HC (P=0.01). Similarly, naïve CD8 T cells were lower with 37.5% (25.7) in ACHDET vs 62.8% (22.9) in HC (P=0.02). This also resulted in a reciprocal increase in memory CD4 and CD8 T Cells in the ACHD-ET group. The ACHD-NT was not significantly different than the other groups. The frequencies of influenza antigen-specific memory CD4 T cells expressing IFN-γ and TNF-α were significantly increased in post-vaccine blood samples compared to pre-vaccine samples across all 3 groups (P<0.05). Conclusions: ACHD-ET have a smaller population of naïve T cells, suggestive of immunosenescence. Despite this they have an equivalent cytokine response suggesting that early thymectomy does not inhibit the response to vaccination in young adulthood. Our findings support the recommendation that preventative vaccination against pathogens including influenza virus and the newly emerging SARS-CoV-2 should continue to be routinely performed in ACHD.