Development of Fetal Thymocytes in Organ Cultures

When mature thymus-derived (T) lymphocytes from peripheral lymphoid organs are activated by antigen or mitogen, an increase in the expression of the surface receptor for interleukin 2 (IL-2-R) is observed that precedes the development of effector function (1-3). While IL-2 is known to be a specific growth factor for such mature T cells (4, 5), it is not known whether IL-2 is also involved as a regulatory molecule in the early maturation of thymocytes (6-9). It has recently been reported that the IL-2-R can be detected on cells in the fetal thymus at day 13 of gestation, and by day 14, >90% of fetal thymocytes are IL2-R+ (6-8). Little is known of the origin of fetal thymocyte precursors or the events controlling their development. Several questions arise from the finding of such a high proportion of Thy-I', IL-2-R+ thymocytes in the day-14 fetus . First, is IL-2 involved in regulating the maturation of these cells? Second, are cells in the 14-day fetal thymus capable of synthesizing IL-2? There are several remarkable changes that occur in the fetal thymus . While the phenotype of most cells on day 14 of gestation is Thy-I', IL2-R+ , by day 16 this has changed so that a majority of cells are Thy-I', L3T4+, Ly-2+, IL-2-R(6, 7) . In addition, the events that are associated with the development of antigen specificity and MHC restriction of effector function appear to occur as L3T4+, Ly-2+ cells emerge (10-16). Organ culture of murine fetal thymus lobes at day 14 of gestation has been successfully used to follow the maturation of thymocyte precursors that have already seeded this tissue (11, 13, 17). The progression of Thy-I', IL-2-R', cells to Thy-I', L3T4+, Ly-2+ cell populations can be followed over a period of days in vitro (13, 17, 18). The organ culture system has potential for the purpose of analyzing the mechanisms that control thymocyte maturation. We describe here the influence of IL-2 on fetal thymocyte development. When IL-2 is added to organ cultures on 14-d fetal thymic lobes, an inhibition of thymocyte proliferation is observed and the development of Thy-I', L3T4+, Ly-2+ cells is impaired . A population of IL-2-activated cytotoxic cells emerge . This report summarizes the kinetics of