Studies in animal models first revealed a potential association of multifunctional Th1 cells with protective immunity to TB [18], but recent studies in humans assessing differences in multifunctional T cell cytokine production in active PTB (compared with latent TB) have shown increased antigen-specific multifunctional CD4+ T cells [21], [22], [32], decreased frequencies [19], [20], or no difference [33]. This evidence concerns the gene CD4 and tuberculosis.