02952nas a2200421   4500000000100000008004100001260001300042653002400055653002000079653003000099653004400129653001100173653002300184653001800207653002600225653001200251653001600263653001400279653001800293653002400311653002500335653002500360653002900385653001900414653001500433100001300448700001500461700001500476700001300491700001400504700001700518700001600535245013500551300001100686490000700697520181200704022001402516       1990                            d  c1990 Dec10aAntigens, Bacterial10aCell Separation10aCytotoxicity, Immunologic10aDose-Response Relationship, Immunologic10aHumans10aImmunity, Cellular10aInterleukin-210aKiller Cells, Natural10aleprosy10aMacrophages10aMonocytes10aMycobacterium10aMycobacterium bovis10aMycobacterium leprae10aT-Lymphocyte Subsets10aT-Lymphocytes, Cytotoxic10aTetanus Toxoid10aTuberculin1 aKaleab B1 aOttenoff T1 aConverse P1 aHalapi E1 aTadesse G1 aRottenberg M1 aKiessling R00aMycobacterial-induced cytotoxic T cells as well as nonspecific killer cells derived from healthy individuals and leprosy patients.  a2651-90 v203 a<p>Little information is available about the generation and specificity of the cytotoxic cells that eliminate human monocytes/macrophages infected with mycobacteria. To address this we have developed a cytotoxicity assay in which 51Cr-labeled monocytes pulsed with bacillus Calmette Guerin (BCG) or Mycobacterium leprae, were used as target cells in overnight cytotoxicity assays. As effector cells, peripheral blood mononuclear cells from healthy occupational contacts or from leprosy patients stimulated with antigen for 7 days were used. Cytotoxicity against antigen-pulsed monocytes that could be induced by mycobacterial antigens was proportional to the degree of antigen responsiveness in each individual, as measured in lymphocyte transformation tests. The lepromatous leprosy patients tested were often poor responders to BCG as well as M. leprae, both with regard to induction of cytotoxicity as well as in lympho-proliferation. Killing was significantly higher against antigen-pulsed vs. nonpulsed monocytes, although significant killing was induced against the latter as well and paralleled by induction of natural killer activity against the K-562 target cell. Cross-reactivity was observed between BCG and M. leprae, but not with unrelated antigen (tetanus toxoid) or with endogenous stress proteins induced by heat shock. M. leprae- and BCG-activated cytotoxic cells were found in both the CD4-CD8+ and CD4+CD8- populations, whereas in contrast the soluble antigen, purified protein derivative of M. tuberculosis, generated cytotoxic cells that were exclusively of the CD4+ phenotype. The involvement of both specific T cells as well as nonspecific cells in the killing of human macrophages may be important with respect to protection and immunopathology induced by mycobacterial antigens.</p>  a0014-2980