Aging of the CD4 T Cell Compartment

Abstract

Higher morbidity and mortality following infections, particularly influenza, is observed in the elderly population. Because of this, people over 65 years old are often targeted for preventive immunization. Many vaccines, however, are not as effective in generating protective antibodies in older individuals. CD4⁺ T cells, through their B cell helper functions, play a central role in the humoral response. Aging has deleterious effects on the immune system, and understanding how aging impairs CD4⁺ T cell functions is of critical importance to design new immunization and treatment strategies targeted to the elderly population. In this paper, we review some of the qualitative and quantitative changes in the CD4⁺ T cell compartment that arise with aging. We also summarize the age-related intrinsic defects that impact naïve, memory and regulatory CD4⁺ T cell functions.

Keywords: Age-associated defects; CD4+ T cells.

Fig. 1

In young age (left panel), the thymus generates a large number of naïve CD4⁺ T cells every day. These cells reach the periphery where they form the majority of the CD4⁺ T cell pool, with fewer memory and regulatory CD4⁺ T cells. In old age (right panel), thymic involution leads to a much reduced output of naïve CD4⁺ T cells and a relatively increased output of regulatory T cells. Very few naïve CD4⁺ T cells therefore reach the periphery where memory CD4⁺ T cells, generated through antigen encounters throughout life and other factors (see text), accumulate.