We established an in vitro model of the phagocytosis of Mycobacterium tuberculosis by human peripheral blood monocytes to evaluate the subsequent inhibition of intracellular replication of the organism. Highly purified T cells (94% CD3+/CD16-) or natural killer (NK) cells (96% CD16+/CD3-) isolated by Percoll discontinuous density gradient of peripheral blood mononuclear cells were incubated with M. tuberculosis-infected monocyte monolayers. Monocytes were lysed immediately and at 4, 7, and 10 d after infection for quantification of intracellular replication, which was assessed by quantitative plating techniques as colony-forming units (CFU). Whereas control monocytes permitted intracellular replication, T cells activated monocytes to kill 77% (p <0.01) of intracellular M. tuberculosis compared with control monocytes by 10 d after infection. NK cells activated monocytes to kill 84% (p <0.01) of M. tuberculosis in comparison with control monocytes. Lymphokine (IL-2)-activated-killer (LAK) cells were capable of activating monocytes to kill 97% (p <0.01) of the intracellular organisms compared with control monocytes. In purified protein derivative (PPD)- positive donors, PPD-specific-CD4+ lymphocytes stimulated monocytes to kill intracellular M. tuberculosis in a Class II major histocompatibility complex- restricted manner. In contrast, in PPD-negative donors, CD4- lymphocytes activated monocytes in a genetically unrestricted manner. Both T cell supernatant and NK cell supernatant generated from cocultivation with M. tuberculosis, infected monocytes also activated monocytes to augment mycobactericidal function. In conclusion, T cells, NK cells, LAK cells, and their supernatants activated mycobactericidal function of monocytes, although these pathways of activation differed in terms of antigenic specificity and genetic restriction.
|Original language||English (US)|
|Number of pages||9|
|Journal||American Journal of Respiratory and Critical Care Medicine|
|State||Published - 1998|
ASJC Scopus subject areas
- Pulmonary and Respiratory Medicine