Abstract Interleukin (IL)-2 plays a key role in adjusting the dynamic state of equilibrium between effector T cells (Teffs) and regulatory T cells (Tregs) as well as channeling the outcome of immune responses. IL-2 is mainly produced by activated CD4 T cells and the absence of IL-2 signaling results in lethal autoimmunity. In this study we investigated the role of tumor necrosis factor alpha (TNF) receptors type 1 (TNFR1) and type 2 (TNFR2) on the regulation of IL-2 at the level of transcription during the primary activation of CD4 T cells. We generated TNFR1- and/or TNFR2-deficient-IL-2-GFF knock-in reporter mice to examine Il2 promoter activity at the single cell level. We found that the deficiency of TNFR2, but not TNFR1, markedly diminished the number of CD4 T cells that produced IL-2. We further correlated decreased Il2 transcription with impaired intracellular c-Rel expression in TNFR2 KO CD4 T cells. IL-2 production was augmented in response to the addition of soluble TNF implicating a role for transmembrane TNF (tmTNF). Collectively, these data suggest that CD4 T cell autonomous tmTNF/TNFR2 signaling contributes to the number of IL-2 producers by providing a critical third signal necessary for threshold Il2 promoter activity. These results have important implications for understanding the contribution of IL-2 signaling on the dynamic equilibrium between Teff cells and Treg cells and the outcome of inflammatory immune responses.