Bim dictates naïve CD4 T cell lifespan and the development of age-associated functional defects1

• Published in: The Journal of immunology (1950) 2010-09, Vol.185 (8), p.4535-4544
• Main Authors: Tsukamoto, Hirotake, Huston, Gail E., Dibble, John, Duso, Debra K., Swain, Susan L.
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1001668

With age peripheral naïve CD4 T cells become both longer-lived and functionally impaired and they express reduced levels of Bim, a pro-apoptotic Bcl-family member. In this study, we show that reduced Bim expression by naïve CD4 T cells intrinsically mediates their longer lifespan in the periphery. Moreover, using mixed bone marrow chimeras reconstituted with Bim +/+ and Bim +/− bone marrow cells, Bim +/− naïve CD4 T cells exhibit accelerated development of age-associated dysfunctions including reduced proliferation and IL-2 production and defective helper function for B cells, without any increase in their turnover. However, newly generated Bim +/− naïve CD4 T cells in middle aged mice are not defective, indicating an additional requirement for their persistence in the periphery. These age-associated immune defects develop independently of the “aged” host environment and without extensive division, distinguishing them from classic “senescence”. We suggest that the reduction of Bim levels with age in naïve CD4 T cell is the initiating step that leads to increased cellular lifespan and development of age-associated functional defects.