T helper cells differentiate into functionally distinct effector cell subsets, of which Th1 and Th2 cells are best characterized. Besides TCR signaling, IL-12 induced STAT4 and T-bet and IL-4 induced STAT6 and GATA3 signaling pathways are the major players regulating Th1 and Th2 differentiation process, respectively. However, there are likely to be other yet unknown factors or pathways involved. In this study we have used quantitative proteomics exploiting cICAT labeling and LC-MS/MS to identify IL-4 regulated proteins from the microsomal fractions of CD4+ cells extracted from umbilical cord blood. We were able to identify 557 proteins, of which 304 were also quantified. This study resulted in identification of small GTPases GIMAP1 and GIMAP4 to be downregulated by IL-4 during Th2 differentiation. We also showed that both GIMAP1 and GIMAP4 genes are upregulated by IL-12 and other Th1 differentiation inducing cytokines in cells induced to differentiate towards Th1 lineage and downregulated by IL-4 in cells induced to Th2. Our results indicate that the GIMAP family of proteins is differentially regulated during Th cell differentiation.