Effects of T‐cell derived Leptin on Thymic Function and Immune Regulation

Abstract

The communication between the state of systemic and cellular energy balance to the immune compartment is mediated via a complex array of cytokines, hormones and neuropeptides. Leptin is an adipocyte-derived hormone and belongs structurally to the cytokine family including members such as IL-2 and IL-12. Leptin signals via a class I cytokine receptor and represents an important link between energy balance on the one side and immune function on the other. Leptin has recently been shown to be produced in limited quantities by murine T cells. To examine the endogenous role of this hormone in the development and control of the adaptive immune responses and inflammation, we have generated T-cell transgenic mice overexpressing leptin. Leptin overexpression in T cells affects thymic size and cellularity and may have considerable impact on the immune function of aging mice. Preliminary data shows that leptin affects CD4−CD8−, CD4+CD8+, CD8+ thymocyte numbers and differentially affects double negative thymocyte subpopulations, increasing ETPs, Lin-CD44+CD25+, Lin-CD44−CD25+ thymocyte numbers in leptin transgenic mice when compared to wild-type controls. Also, naïve CD44−CD62+ T cell production in spleen was significantly lower in leptin transgenic mice, suggesting that endogenously produced leptin may play an important role in thymic development with age.