Leptin can enhance thymopoiesis and modulate the T-cell immune response However, it remains controversial whether these effects correlate with the expression of leptin receptor. ObR We herein addressed this issue by using in vivo animal models and in vitro culture systems Leptin treatment in both ob/ob mice and normal young mice induced increases of CD4 SP thymocytes in thymus and CD4 T cells in the periphery Interestingly, expression of the long form ObR was significantly restricted to DN, DP and CD4 SP, but not CD8 SP thymocytes Moreover, in the reaggregated DP thymocyte cultures with leptin plus TSCs, leptin profoundly induced differentiation of CD4 SP but not CD8 SP thymocytes, suggesting that the effects of leptin on thymocyte differentiation might be closely related to the expression of leptin receptor in developing thymocytes Surprisingly, ObR expression was markedly higher in peripheral CD4 T cells than that in CD8 T cells Furthermore, leptin treatment with or without IL-2 and PHA had preferential effects on cell proliferation of CD4 T cells compared to that of COB T cells Collectively, these data provide evidence that the effects of leptin on differentiation and proliferation of CD4 T cells might be closely related to the expression of leptin receptor (C) 2010 Elsevier Inc All rights reserved