The aged lymphoid tissue environment fails to support naïve T cell homeostasis

• Published in: Scientific reports Vol. 6; no. 1; p. 30842
• Main Authors: Becklund, Bryan R, Purton, Jared F, Ramsey, Chris, Favre, Stéphanie, Vogt, Tobias K, Martin, Christopher E, Spasova, Darina S, Sarkisyan, Gor, LeRoy, Eric, Tan, Joyce T, Wahlus, Heidi, Bondi-Boyd, Brea, Luther, Sanjiv A, Surh, Charles D
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 02.08.2016
• Subjects: Animals; Cell Proliferation; Chemokines; Homeostasis; Homeostasis - physiology; Immunologic Memory - immunology; Immunological memory; Interleukin 7; Lymphocyte Activation - immunology; Lymphocytes; Lymphocytes T; Lymphoid tissue; Lymphoid Tissue - immunology; Memory cells; Mice; Mice, Inbred C57BL; Spleen; Survival; T cell receptors; T-Lymphocyte Subsets - immunology; Thymus
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep30842

Aging is associated with a gradual loss of naïve T cells and a reciprocal increase in the proportion of memory T cells. While reduced thymic output is important, age-dependent changes in factors supporting naïve T cells homeostasis may also be involved. Indeed, we noted a dramatic decrease in the ability of aged mice to support survival and homeostatic proliferation of naïve T cells. The defect was not due to a reduction in IL-7 expression, but from a combination of changes in the secondary lymphoid environment that impaired naïve T cell entry and access to key survival factors. We observed an age-related shift in the expression of homing chemokines and structural deterioration of the stromal network in T cell zones. Treatment with IL-7/mAb complexes can restore naïve T cell homeostatic proliferation in aged mice. Our data suggests that homeostatic mechanisms that support the naïve T cell pool deteriorate with age.