02140nas a2200325 4500000000100000008004100001260001300042653001200055653002000067653001100087653004100098653002600139653003700165653000900202653001200211653003100223653001800254653001700272653001100289100001300300700001700313700001300330700001400343700001700357245009900374300001100473490000700484520130900491022001401800 1985 d c1985 Feb10aAnimals10aCells, Cultured10aFemale10aHistocompatibility Antigens Class II10aMacrophage Activation10aMajor Histocompatibility Complex10aMice10aMitosis10aMycobacterium tuberculosis10aT-Lymphocytes10aTuberculosis10aUracil1 aRook G A1 aChampion B R1 aSteele J1 aVarey A M1 aStanford J L00aI-A restricted activation by T cell lines of anti-tuberculosis activity in murine macrophages. a414-200 v593 a

Tuberculosis and leprosy remain two of the world's most significant diseases. Immunity involves the activation of macrophages by lymphokines but the details are unknown because there has been no objective assay for the relevant effector function using human pathogens. We previously reported the use of tritiated-uracil uptake by surviving mycobacteria as a measure of the anti-mycobacterial effect of human monocytes. We describe here the use of a modification of this assay to measure control of the proliferation of Mycobacterium tuberculosis in murine peritoneal macrophages. A bacteriostatic effect can be induced in macrophages infected with M. tuberculosis, by adding small numbers of Ly 1 +2- T cells from in vitro lines derived from immunized mice. The phenomenon is dependent on compatibility at the I-A locus of the major histocompatibility complex (MHC) and mediated by soluble factors. Such T cells also recognise and activate macrophages infected with other mycobacterial pathogens. Thus, T cells recognising shared mycobacterial antigens are active. The findings have implications for MHC linked susceptibility to mycobacterioses and the hypothesized ability of cross-reactive environmental mycobacteria to abrogate or pre-empt the protective efficacy of subsequent BCG vaccination.

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