I-A RESTRICTED ACTIVATION BY T-CELL LINES OF ANTI-TUBERCULOSIS ACTIVITY IN MURINE MACROPHAGES

Abstract

Tuberculosis and leprosy remain 2 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. The use of 3H-uracil uptake by surviving mycobacteria as a measure of the anti-mycobacterial effect of human monocytes was previously reported. The use of a modification of this assay to measure control of the proliferation of Mycobacterium tuberculosis in murine peritoneal macrophages is not reported. 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 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 recognize and activate macrophages infected with other mycobacterial pathogens. Thus, T cells recognizing shared mycobacterial antigens are active. The findings have limitations for MHC linked-susceptibilty to mycobacterioses and the hypothesized ability of cross-reactive environmental mycobacteria to abrogate or pre-empt the protective efficacy of subsequent BCG vaccination.