title: The aged lymphoid tissue environment fails to support naïve T cell homeostasis.
abstract: 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.
authors.affiliation: Department of Developmental Immunology, La Jolla Institute for Allergy and Immunology, La Jolla, CA, 92037, USA.|Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA, 92037, USA.
authors.forename: Bryan R
authors.initials: BR
authors.lastname: Becklund
authors.affiliation: Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA, 92037, USA.
authors.forename: Jared F
authors.initials: JF
authors.lastname: Purton
authors.affiliation: Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA, 92037, USA.
authors.forename: Chris
authors.initials: C
authors.lastname: Ramsey
authors.affiliation: Department of Biochemistry, Center for Immunity and Infection, University of Lausanne, 1066 Epalinges, Switzerland.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Favre
authors.affiliation: Department of Biochemistry, Center for Immunity and Infection, University of Lausanne, 1066 Epalinges, Switzerland.
authors.forename: Tobias K
authors.initials: TK
authors.lastname: Vogt
authors.affiliation: Department of Developmental Immunology, La Jolla Institute for Allergy and Immunology, La Jolla, CA, 92037, USA.|Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA, 92037, USA.
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Martin
authors.affiliation: Department of Developmental Immunology, La Jolla Institute for Allergy and Immunology, La Jolla, CA, 92037, USA.|Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA, 92037, USA.
authors.forename: Darina S
authors.initials: DS
authors.lastname: Spasova
authors.affiliation: Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA, 92037, USA.
authors.forename: Gor
authors.initials: G
authors.lastname: Sarkisyan
authors.affiliation: Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA, 92037, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: LeRoy
authors.affiliation: Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA, 92037, USA.
authors.forename: Joyce T
authors.initials: JT
authors.lastname: Tan
authors.affiliation: Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA, 92037, USA.
authors.forename: Heidi
authors.initials: H
authors.lastname: Wahlus
authors.affiliation: Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA, 92037, USA.
authors.forename: Brea
authors.initials: B
authors.lastname: Bondi-Boyd
authors.affiliation: Department of Biochemistry, Center for Immunity and Infection, University of Lausanne, 1066 Epalinges, Switzerland.
authors.forename: Sanjiv A
authors.initials: SA
authors.lastname: Luther
authors.affiliation: Department of Developmental Immunology, La Jolla Institute for Allergy and Immunology, La Jolla, CA, 92037, USA.|Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA, 92037, USA.|Academy of Immunology and Microbiology, Institute for Basic Science, Pohang, Republic of Korea.|Department of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, Republic of Korea.
authors.forename: Charles D
authors.initials: CD
authors.lastname: Surh
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D006706:Homeostasis / Q000502:physiology*; D007156:Immunologic Memory / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D008221:Lymphoid Tissue / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016176:T-Lymphocyte Subsets / Q000276:immunology*