The second hypothesis suggests BCG stimulates helper T1 and helper T17 immune cell polarization and generation of memory CD4+ and memory NK cells; upon secondary infection with a nonmycobacterial pathogen, these memory cells undergo bystander lymphocyte activation because less stimulus is required.29 The third hypothesis is trained immunity, in which innate immune cells have analogous durable memory responses to unrelated secondary antigens as a result of epigenetic remodeling on primary exposure. Here, CD4 is linked to infection.