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

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.