Differential interferon-gamma production potential among naïve CD4⁺ T cells exists prior to antigen encounter

Individual CD4⁺ T cells can become one of a number of helper (Th) lineages with distinct effector functions. However, whether biases in Th potential exist prior to antigen encounter is unknown. Studies have identified cell-intrinsic functional heterogeneity among naïve T cells that can be parsed based on the strength of T-cell receptor (TCR) interactions with self-peptide. Here, using CD5 levels as a surrogate for the strength of these basal TCR signals, we sought to identify pre-existing effector biases in the CD4⁺ T-cell lineage. We show that ex vivo-activated CD5^lo CD4⁺ T cells produce greater amounts of the Th1 cytokine interferon-gamma (IFNγ) than their CD5^hi counterparts. In addition, a greater percentage of CD5^lo effector CD4⁺ T cells produce IFNγ in both polyclonal and monoclonal CD4⁺ T-cell populations after antigen challenge in vivo. These results suggest that differential IFNγ production potential exists among CD4⁺ T cells prior to activation and independent of TCR affinity for foreign antigen.