CD28 and TCR differentially impact Naïve and Memory T cell responses

Manipulating CD28 co-stimulation is a key element of anti-tumour immune responses and treating autoimmune diseases. CD28 can reduce the T cell activation threshold but has a complex relationship with TCR signalling and an unclear role in specific T cell subsets. Using a series of in vitro stimulation assays, we have studied the relative contribution of CD28 and TCR signals in human CD4+ T cell responses. We show that not only the quantity of CD28 co-stimulation, but also its intensity relative to TCR differentially impacts division of Naïve and Memory T cells. We show that CD28 co-stimulation can have TCR independent effects on Memory T cell phenotype and cytokine production and in some settings can antagonise TCR-driven functions. These data highlight the complex relationship between CD28 co-stimulation and TCR signals and expose clear differences in their use by Naïve and Memory T cells.