Human thymic stromal cell irradiation reduces intra-thymic T cell precursor proliferation: evidence for a soluble mediator

PURPOSE: To investigate the effects of ionizing radiations on human thymic stromal cells and the consequences of stromal cell irradiation on T cell precursor proliferation. MATERIAL AND METHODS: An in vitro model of thymic stromal cell culture was used. These cultures are able to support early CD7high T cell precursor proliferation and differentiation, mainly towards a CD3+TcRgamma+CD8+ pathway, in the presence of interleukin-7 and stem cell factor. Thymic stromal cell cultures were exposed to 10 Gy 60Co gamma-rays, 24 h before the seeding of CD7high T cell precursors. RESULTS: Irradiation of thymic stromal cells induced a reduction in CD7high T cell precursors, without modifying their differentiation. This effect was reproduced by the addition of supernatants from irradiated stromal cell cultures in sham-irradiated cultures. CONCLUSIONS: These results suggest that gamma-irradiation induces modifications in the production of soluble factors by thymic stromal cells, which in turn modify their ability to support T cell precursor proliferation. To the authors' knowledge this is the first direct demonstration that gamma-irradiation modifies the supportive function of thymic stromal cells.