(900) Impact of Thymus Removal in Altering CD8 T Cell Properties

Introduction/Rationale: The thymus supplies naïve T cells to sustain T cell populations, but it gradually shrinks with age, leading to a decline in thymic output. Consequently, cessation of thymic output reduces naïve T cell numbers, raising the question of whether the remaining cells adapt to maintain immune competence.

Methods: Here, we examined the quantity and quality of antigen-specific CD8 T cells in mice after thymectomy.

Results: Our experiments showed that thymectomy reduced the number of antigen-specific CD8 T cells. Interestingly, following acute lymphocytic choriomeningitis virus (LCMV) infection, antigen-specific CD8 T cells derived from thymectomized mice exhibited greater expansion and generated more memory cells than those from controls. To explore why CD8 T cells from thymectomized mice possess such augmented expansion capacity, we analyzed these CD8 T cells prior to infection and found significant phenotypic remodeling after thymectomy, thereby altering their subset composition. Virtual memory (VM) cells, which exhibits memory phenotypes yet remain antigen inexperienced, increased within the antigen-specific CD8 T cell pool after thymectomy. In addition, thymectomy altered the phenotypes of antigen-specific naïve CD8 T cells, greatly enriching the IL-18Rα⁺ CD73⁺ CXCR3⁺ subset. Importantly, this subset contributed to the enhanced expansion of antigen-specific CD8 T cells after LCMV infection.

Conclusion: Together, our findings suggest that upon loss of thymic output during thymic involution or thymectomy, antigen-inexperienced CD8 T cells undergo qualitative remodeling, compensating for reduced cell numbers by increasing functionally potent subsets that help preserve antiviral immunity.