IL-7 gene therapy in aging restores early thymopoiesis without reversing involution

JA Phillips, TI Brondstetter, CA English… - The Journal of …, 2004 - journals.aai.org
JA Phillips, TI Brondstetter, CA English, HE Lee, EL Virts, ML Thoman
The Journal of Immunology, 2004journals.aai.org
Thymic involution begins early in life and continues throughout adulthood, resulting in a
decreased population of naive T cells in the periphery and a reduced ability to fight off newly
encountered infectious diseases. We have previously shown that the first step of
thymopoiesis is specifically blocked in aging. This block at the DN1 to DN2 transition and the
subsequent loss of thymic output in old age mirrors the changes seen in IL-7-deficient mice,
and it is hypothesized that decreased intrathymic IL-7 is involved in age-related thymic …
Abstract
Thymic involution begins early in life and continues throughout adulthood, resulting in a decreased population of naive T cells in the periphery and a reduced ability to fight off newly encountered infectious diseases. We have previously shown that the first step of thymopoiesis is specifically blocked in aging. This block at the DN1 to DN2 transition and the subsequent loss of thymic output in old age mirrors the changes seen in IL-7-deficient mice, and it is hypothesized that decreased intrathymic IL-7 is involved in age-related thymic involution. To separate the effect of IL-7 on thymic involution from its function as a peripheral lymphocyte growth cofactor, we injected IL-7-secreting stromal cells into the thymi of recipient mice. The increased local concentration of IL-7 maintained the first step of thymopoiesis at a level far higher than was seen in age-matched controls. However, despite this success, there was no decrease in thymic involution or increase in T cell output. The inability of IL-7 to prevent involution led us to the discovery of an additional age-sensitive step in thymopoiesis, proliferation of the DN4 population, which is unaffected by IL-7 expression.
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