To determine the role of leptin signaling in driving T cell inflammation in the context of obesity-associated changes in systemic metabolism, we generated T cell-specific leptin receptor knockout mice by crossing leptin receptor floxed (LepRfl/fl) animals with mice expressing a Cre recombinase transgene under the control of the CD4+ promoter (CD4Cre) on the C57BL/6 background, as we have previously described [29,30]. Here, CD4 is linked to obesity due to melanocortin 4 receptor deficiency.