Deprivation of leukemia inhibitory factor by its function-blocking antibodies augments T cell activation

Leukemia inhibitory factor (LIF) is a cytokine that acts on a wide range of cell types in vitro, but knowledge of its physiological role is limited. High levels of LIF protein have been selectively detected in the thymus throughout postnatal development. LIF-deficient mice have shown impaired thymic T cell maturation, suggesting the possibility that T cells require LIF for maturation. We have used highly specific antibodies raised against native rat LIF to inhibit LIF function during a defined and restricted period of thymic T cell maturation (first postnatal week). Surprisingly, we observed increased T cell activation in the LIF-deprived wild-type rat. The increased T cell response is retained even 4 weeks after anti-LIF treatment when the level of LIF in the thymic microenvironment has returned to normal. Our results are in contrast to findings with LIF knockout mice, where decreased T cell activation was observed. These observations suggest that LIF may have alternative effects on various phases of T cell development and that LIF may be involved in the restriction of the T cell repertoire during maturation occurring in the first postnatal week.