Given the strong evidence for critical roles for T cells in MDD, namely the elevated ratio of CD4+/CD8+ T cells in MDD patients (Maes et al., 1990) and that T cell deficiency in mice increases maladaptive stress response behaviors which are ameliorated by T cell adoptive transfer (Cohen et al., 2006), antigen presentation and subsequent co-stimulation of T and B cells could have critical impacts on the stress response. Here, CD4 is linked to major depressive disorder.