Some T cells are the immune system's memory chips. Before the immune system can mount an effective attack on a disease-causing microorganism, they must form a subset of "memory" T cells specific for that organism. These "memory" T cells orchestrate immune elimination of the invader and remain in the blood and tissues so that the system can mount another counterattack should the foreign agent invade again. Memory T cell activity is also the key to explaining how vaccines work. Vaccines expose the immune system to weakened or noninfectious forms of pathogens, thus activating T cell memory and tricking the system into generating these critical disease-fighting cells. Researchers in Louis Picker's laboratory focus their studies on memory T cell biology in human and nonhuman primates. They investigate the physiology of T cell memory and effector responses, including mechanisms that control "selection" of the memory repertoire, the functional specialization of the memory population, and the elements involved in T cell homeostasis and regeneration. At the same time, these scientists are seeking to determine the basis of effective immunity to certain chronic human pathogens, particularly HIV/SIV, Mycobacterium tuberculosis, and cytomegalovirus, and are working on prophylactic and/or therapeutic vaccines against these pathogens. Picker and his colleagues have developed special expertise in the quantification and functional characterization of antigen-specific memory T cells. They exploit these technologies in the examination of human subjects and rhesus macaque models of chronic viral infection.