Effect of age on homeostasis of lymphocytes in an interleukin-7-deficient mouse model

Eur Cytokine Netw. 2011 Mar;22(1):63-72. doi: 10.1684/ecn.2011.0273.

Abstract

Interleukin (IL)-7 is thought to be a non-redundant cytokine for lymphopoiesis as there is a reduction of T and B cells in peripheral blood (PB) and a loss of TCRγδ+ cells in PB and bone marrow (BM) in IL-7⁻/⁻ mice. To investigate whether the absence of IL-7 influences the organ-dependent distribution of the lymphocytes, we analyzed single cell suspensions of several organs (BM, lung, liver, small intestine, and spleen) at different ages (three and 12 months) of IL-7+/+ and IL-7⁻/⁻ mice using flow cytometry; immunohistochemical staining was performed on frozen sections of various organs. We observed lymphocytopenia in almost all organs of IL-7⁻/⁻ mice, but normal counts in the liver and the lung of three-month-old IL-7⁻/⁻ mice. CD4+ and CD8+ cell numbers were decreased in the spleen and the BM. With aging, we found a greater increase in CD4+ and CD8+ cells in the BM of IL-7⁻/⁻ than in IL-7+/+ mice, particularly of memory cells. The spleen of IL-7⁻/⁻ mice was characterized by lymphocytopenia. We challenge the view that IL-7 is a non-redundant cytokine for lymphocyte development. Some of the changes observed, e.g. partial absence of TCRγδ+ T cells in the PB, BM and small intestine and complete loss in liver, lung and spleen, may be due to the altered organ distribution instead of a defect in γδ+ T cell lymphopoiesis. In this model, aging leads to a significantly altered composition of lymphocyte subsets, and the lack of IL-7 seems to accelerate this process.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / immunology*
  • Animals
  • Body Weight
  • Bone Marrow / immunology
  • Homeostasis / immunology*
  • Interleukin-7 / deficiency*
  • Interleukin-7 / immunology
  • Intestine, Small / cytology
  • Intestine, Small / immunology
  • Liver / cytology
  • Liver / immunology
  • Lymphocyte Subsets / cytology
  • Lymphocyte Subsets / immunology
  • Lymphocytes / cytology
  • Lymphocytes / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Models, Animal*
  • Organ Specificity / immunology
  • Spleen / cytology
  • Spleen / immunology

Substances

  • Interleukin-7