IL-12 inhibits thymic involution by enhancing IL-7- and IL-2-induced thymocyte proliferation.

Academic Article

Abstract

  • 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, IL-12b knockout (IL-12b(-/-)) mice exhibited accelerated thymic involution compared with wild-type (WT) B6 mice. This is characterized by an increase in thymocytes with the early development stage phenotype of CD25(-)CD44(+)CD4(-)CD8(-) in aged IL-12b(-/-) mice. 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 IL-12b(-/-) mice compared with WT mice. There was, however, no apparent defect in thymic structure and thymocyte development in young IL-12(-/-) mice. These results suggest the importance of IL-12 in maintaining thymic integrity and function during the aging process. Surprisingly, in WT B6 mice, 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 IL-7 or IL-2 induced thymocyte proliferative response, especially in aged WT and IL-12b(-/-) mice. 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.

    • Authors

    Published In

    Keywords

  • Adjuvants, Immunologic, Aging, Animals, Apoptosis, Cell Division, Cells, Cultured, Drug Synergism, Female, Interleukin-12, Interleukin-12 Subunit p40, Interleukin-2, Interleukin-7, Mice, Mice, Inbred C57BL, Mice, Knockout, Protein Subunits, Signal Transduction, T-Lymphocyte Subsets, Thymus Gland

    • Pubmed Id

  • 23540262

    • Author List

  • Li L; Hsu H-C; Stockard CR; Yang P; Zhou J; Wu Q; Grizzle WE; Mountz JD

    • Start Page

  • 2909

    • End Page

  • 2916

    • Volume

  • 172

    • Issue

  • 5