title: IL-12 influences intrathymic T cell development.
abstract: IL-12 has been implicated in the maturation and activation of peripheral T lymphocytes and NK cells. In the present study we have investigated the potential role of IL-12 in intrathymic T cell development. Treatment of mouse fetal thymic organ culture with IL-12 caused a significant reduction in size and cell number compared with the untreated controls. Flow cytometric analysis of the thymocytes recovered from these lobes showed differential effects on individual thymocyte subsets, most but not all of which were significantly decreased. In contrast, however, we observed an increase in both the percentage and cell number of alpha beta TCR+CD4-CD8+ thymocytes. This effect could be neutralized with an anti-IL-12 antibody, demonstrating the specificity of the influence of IL-12 in the fetal thymic organ culture system. IL-12 caused proliferation of isolated thymocyte subsets, particularly CD3+CD4-CD8+ cells in the presence of IL-2 and IL-4. Additionally, IL-12 induced significant proliferation of early CD3-CD4-CD8- triple negative CD44+CD25+ pro-T cells in combination with stem cell factor. We show that both the p35 and p40 chains of IL-12 are produced in the fetal and adult mouse thymus and that thymic stromal cells are a potential source of this cytokine.
authors.affiliation: DNAX Research Institute, Palo Alto, CA 94304.
authors.forename: D I
authors.initials: DI
authors.lastname: Godfrey
authors.forename: J
authors.initials: J
authors.lastname: Kennedy
authors.forename: M K
authors.initials: MK
authors.lastname: Gately
authors.forename: J
authors.initials: J
authors.lastname: Hakimi
authors.forename: B R
authors.initials: BR
authors.lastname: Hubbard
authors.forename: A
authors.initials: A
authors.lastname: Zlotnik
mesh_terms: D000818:Animals; D001483:Base Sequence; D005260:Female; D016298:Hematopoietic Cell Growth Factors / Q000494:pharmacology; D018664:Interleukin-12; D007378:Interleukins / Q000235:genetics / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009924:Organ Culture Techniques; D011247:Pregnancy; D012333:RNA, Messenger / Q000032:analysis; D019089:Stem Cell Factor; D017154:Stromal Cells / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects* / Q000502:physiology; D013950:Thymus Gland / Q000502:physiology
chemical_list: D016298:Hematopoietic Cell Growth Factors; D007378:Interleukins; D012333:RNA, Messenger; D019089:Stem Cell Factor; D018664:Interleukin-12