Assessment of Lymph Node Stromal Cells as an Underlying Factor in Age-Related Immune Impairment

J Gerontol A Biol Sci Med Sci. 2019 Oct 4;74(11):1734-1743. doi: 10.1093/gerona/glz029.

Abstract

Aging negatively impacts immunity, resulting in inefficient responses to vaccinations and infections. Fibroblastic reticular cells (FRCs) are the major stromal cell subset in lymph nodes (LNs) and play an intricate role in the orchestration and control of adaptive immune responses. Although stromal cells have a major impact on immune responses, the impact of aging on LN stromal cells remains unclear. Quantitative analysis of LN stromal cells by flow cytometry revealed that there are no significant differences in the number of stromal cells in young and aged LN at steady state but after influenza infection aged FRCs have delayed expansion as a result of reduced proliferation. Aged LNs also produce reduced levels of homeostatic chemokines, which correlates with reduced homing of naive T cells. Image analysis reveals that young and aged T-cell zone FRCs have similar morphology at steady state and after infection. Furthermore, aged FRCs did not appear to be a contributing factor in the reduced proliferation of young T cells transferred into aged LNs after influenza infection. These results demonstrate that aging alters LN stromal cell response to challenge and these age-related changes may be an underlying contributor to impaired immune responses in the elderly people.

Keywords: Immunity; Influenza; T cells.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aging / immunology*
  • Analysis of Variance
  • Animals
  • Cell Proliferation / physiology
  • Cells, Cultured
  • Chemokines / immunology*
  • Chemokines / metabolism
  • Disease Models, Animal
  • Enzyme-Linked Immunosorbent Assay
  • Fibroblasts / cytology
  • Fibroblasts / physiology
  • Flow Cytometry / methods
  • Immune System Diseases / genetics*
  • Immune System Diseases / immunology
  • Lymph Nodes / immunology
  • Lymph Nodes / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Orthomyxoviridae / pathogenicity*
  • Stromal Cells / immunology*
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism

Substances

  • Chemokines