Impaired Maturation and Survival of T Lymphocytes, B Lymphocytes, and NK Cells in Mice Lacking Gimap5/Ian5.

In biobreeding rats (BB), the lyp mutation in Gimap5/Ian5 is associated with T-cell lymphopenia and autoimmune insulinitis. To delineate the role of Gimap5 in peripheral T cell survival, we generated Gimap5-deficient mice by targeted disruption. Gimap5−/− mice are viable to adulthood, but develop fulminant autoimmune hepatitis, become moribund, and die at a median age of 12 weeks. Gimap5−/− mice are lymphopenic, displaying an overall 7-fold reduction in peripheral T cells and a 43-fold reduction in peripheral CD8+ T cells. Additionally, Gimap5−/− mice exhibit an early, complete block in both NK and NKT lineage development and a partial block in B cell commitment to T1, T2, and mature subsets. Data from lethally irradiated congenic strains reconstituted with Gimap5−/− bone marrow will also be presented. Taken together, these data indicate that Gimap5 is necessary for peripheral survival of T lymphocytes and development of B lymphocytes and NK cells. Furthermore, these data suggest that Gimap5 deficiency plays a role in the development of autoimmune pathology in the mouse.