Taken together, these findings show that the phenotypic differentiation of naïve CD4+ T cells directly influences the pro‐ versus anti‐inflammatory functions of the T cell response to acute brain injury and suggests strategies that aim to reduce effector CD4+ T cell differentiation while promoting Treg expansion may prove beneficial in TBI by augmenting the neuroprotective aspects of this response. The gene discussed is CD4; the disease is brain injury.