Primary and long-term thymocyte cultures were used to analyze intrathymic T-lymphocyte precursors (TLP), the targets of thymocyte growth factor (THGF). It is shown that THGF has an effect on TLP not only as a growth factor, but also, and first of all, as an activation factor, triggering autocrine TLP proliferation. This is realized through secondary products, such as IL-2, IL-3, and THGF of endogenous origin, secreted by the THGF target cells. The intrathymic TLP that respond to THGF are resistant to high doses of irradiation (up to 50 Gy), and because they are in a quiescent state they can remain viable for long periods under unfavourable culture conditions. These TLP are apparently the self-renewing stem cells of the thymus, and are probably involved in the regeneration of this organ under extreme and adverse conditions, providing TLP of other types with growth factors. Data are presented which suggest that proliferation of the THGF target cells is realized in an unusual way, combining formation of daughter cells within the mother cell with ordinary mitosis.

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