Thymocyte specific interleukin-7 restores T cell development but not homeostasis in IL-7KO mice (160.6)

Abstract

Abstract T cells are critically dependent on interleukin-7 (IL-7) as IL-7-deficient mice fail to generate and maintain a functional T cell compartment. Importantly, IL-7 is not produced by T cells and it is only provided by dendritic cells, stromal cells and other non-T cells in trans. Using an lck-proximal enhancer/promoter driven IL-7 transgene (IL-7Tg), here we tested whether T-lineage specific expression of IL-7 can restore T cell development in IL-7 deficient mice. We found that T cell development was completely restored in IL-7Tg.IL-7KO mice as thymocyte numbers, thymic selection, and CD4/CD8 lineage differentiation were identical to WT mice. Importantly, however, IL-7Tg.IL-7KO mice were peripheral T lymphopenic with less than 20% of T cell numbers compared to WT controls. This was presumably induced by termination of transgenic IL-7 expression upon positive selection as qPCR analysis showed a rapid downregulation of IL-7 mRNA expression in mature thymocytes. Surprisingly, the few surviving peripheral T cell in IL-7Tg.IL-7KO mice did not show upregulation of activated or memory T cell markers,and we did not observe any autoimmunity. Further characterization of the function and phenotype of these T cells are currently under progress. Collectively, these data show that IL-7 expression and signaling in cis is sufficient for normal T cell development, and they show in a new in vivo model of peripheral T lymphopenia that continuous IL-7 is critical T cell homeostasis.