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 T cell receptor (TCR) signalling and an unclear role in specific T cell subsets. Using a series of 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 the 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 antagonize 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.