Lysis of mycobacteria-infected monocytes by IL-2-activated killer cells: role of LFA-1.
Mycobacterium avium-intracellulare (MAI) is a ubiquitous soil contaminant that rarely causes disseminated disease in adults regardless of immunological status. In AIDS patients, however, this organism 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, are under the control of natural killer (NK) cells. Autologous large granular lymphocytes (LGL), purified from human peripheral blood leukocytes, were capable of efficiently lysing autologous MAI-infected monocytes in a 5-hr 51Cr release assay. More importantly, interleukin 2 (IL-2) was able to activate the LGL to a higher degree of lysis of infected monocytes. LGL cultured in medium alone could not kill normal monocytes, but showed some degree of lysis of MAI-infected cells. IL-2 activated killer (LAK) cells, on the other hand, lysed normal monocytes to a moderate degree and this activity was makedly enhanced if the monocytes were infected with MAI. The sensitivity of monocytes was directly proportional to the inoculating number of bacteria, indicating that increased bacterial burden would enhance susceptibility to LAK-mediated lysis. Finally, the addition of monoclonal antibodies to LFA-1 (both alpha and beta chains), but not LFA-2 or LFA-3, blocked lysis of both infected and uninfected monocytes when added directly to the cytotoxicity assays, indicating that this adhesion protein is involved in the lysis of autologous, infected monocytes. Thus, NK/LAK cells may be important in containment of infection by lysis of infected monocytes before the bacteria can multiply and spread to other sites.
Blanchard
D K
DK
Department of Medical Microbiology & Immunology, University of South Florida College of Medicine, Tampa 33612.
Michelini-Norris
M B
MB
Friedman
H
H
Djeu
J Y
JY
D000943:Antigens, Differentiation / Q000502:physiology*; D003602:Cytotoxicity, Immunologic; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000276:immunology*; D016169:Lymphocyte Function-Associated Antigen-1; D009000:Monocytes / Q000276:immunology* / Q000382:microbiology; D015270:Mycobacterium avium-intracellulare Infection / Q000276:immunology*; D010641:Phenotype
D000943:Antigens, Differentiation; D007376:Interleukin-2; D016169:Lymphocyte Function-Associated Antigen-1