Figure 6. Potential role of the thymus impacting the CD4/CD8 ratio in the older population. The CD4/CD8 ratio may reflect the overall immune status in older people and hence be associated with the development of comorbidities and the risk of mortality in this population. Many factors have been described to impact the CD4/CD8 ratio. We propose a major role of the thymus and, specifically, its capacity to generate and maintain the functional capacities of both the CD4 and CD8 T-cell compartments; however, it is conceivable that, as an endocrine gland, the thymus also impacts the CD4/CD8 ratio through peripheral immunomodulatory effects. A proper adaptive immune response requires activation of CD4 T cells and their differentiation to helper cells, which will ultimately promote CD8 T cell activation. Adequate thymic output would guarantee the functionality of both T-cell subsets and may control clonal expansions of both subsets, probably favoring the maintenance of adequate relative proportions. Alternatively, dysfunctional helper activity of the CD4 T-cell pool due to reduced thymic function might contribute to the expansion and exhaustion of the CD8 T-cell compartment to compensate for the lack of response, leading to a reduction in the CD4/CD8 ratio.