IL-12 inhibits thymic involution by enhancing @entity10191 - and XXXX -induced thymocyte proliferation.

@entity12782 @entity10191 @entity2047 @entity19 @entity3783 @entity3844
IL-12 has been reported to affect thymic T cell selection, but the role of IL-12 in thymic involution has not been studied. We found that in vivo, @entity12782 knockout ( @entity12782 (-/-)) @entity19 exhibited accelerated thymic involution compared with wild-type (WT) B6 @entity19 . This is characterized by an increase in thymocytes with the early development stage phenotype of @entity3783 (-) @entity3844 (+)CD4(-)CD8(-) in aged @entity12782 (-/-) @entity19 . Histologically, there were accelerated degeneration of thymic extracellular matrix and blood vessels, a significantly decreased thymic cortex/medulla ratio, and increased apoptotic cells in aged @entity12782 (-/-) @entity19 compared with WT @entity19 . There was, however, no apparent defect in thymic structure and thymocyte development in young IL-12(-/-) @entity19 . These results suggest the importance of IL-12 in maintaining thymic integrity and function during the aging process. Surprisingly, in WT B6 @entity19 , there was no age-related decrease in the levels of IL-12 produced from thymic dendritic cells. Stimulation of thymocytes with IL-12 alone also did not enhance the thymocyte proliferative response in vitro. IL-12, however, provided a strong synergistic effect to augment the @entity10191 or @entity2047 induced thymocyte proliferative response, especially in aged WT and @entity12782 (-/-) @entity19 . Our data strongly support the role of IL-12 as an enhancement cytokine, which acts through its interactions with other cytokines to maintain thymic T cell function and development during aging.
