Therefore, we limited our review to articles that referred to induction of IFN-γ+TNF-α+IL-2+ polyfunctional CD4+ T cells in the context of TB vaccination and vaccine immunogenicity in pre-clinical and clinical studies and focused on reviewing the published evidence that polyfunctional CD4+ T cells represent a mechanistic correlate of protection for TB vaccines. The gene discussed is CD4; the disease is tuberculosis.