Cytokine activation of killer cells in mycobacterial immunity

Mycobacterium avium-intracellulare (MAI) is an ubiquitous soil contaminant that rarely causes disseminated disease in adults, regardless of immunological status. In AIDS patients, however, this microorganism invades virtually every tissue and organ, and most conventional chemotherapeutic agents are usually ineffective against MAI. We report here that monocytes, in which MAI has established an intracellular parasitic stage, appear to be under the control of natural killer (NK) cells. Autologous large granular lymphocytes (LGL), purified from human peripheral blood mononuclear cells (PBMC), were capable of efficiently lysing MAI-infected monocytes in a 5 hr 51Cr-release assay. More importantly, interleukin 2 (IL-2) was able to activate the LGL to a high degree of lysis of infected monocytes. Additionally, 3 to 4 days of incubation of LGL with MAI resulted in the induction of killer cells capable of killing bacterially-infected monocytes, as well as tumor cells. Northern blot analysis of RNA from MAI-stimulated LGL revealed specific messages for both IL-2 receptor proteins (p55 and p70). Thus, MAI can directly activate killer cells, which may therefore play a role in containment of MAI infection by lysis of parasitized monocytes before the bacteria can multiply and spread to other sites.