In humans, multifunctional T-cells have been shown to contribute to the efficacy of smallpox vaccines [103] and have also been proposed to play an important role in vaccination against Mycobacterium tuberculosis (TB) using BCG and viral vectors [104], although the relevance of polyfunctional CD4+ T-cells in serving as a correlate of protective immunity for TB has recently been challenged [105]. This evidence concerns the gene CD4 and tuberculosis.