Specific lysis of Listeria monocytogenes‐infected macrophages by class II‐restricted L3T4⁺ T cells

Abstract

Mice were infected with the intracellular bacterium, Listeria monocytogenes, and T cell clones from spleens, lymph nodes and peritoneal exudates were established. The capacity of L3T4+, Lyt2- T-cell clones to specifically lyse L. monocytogenes-infected macrophages was analyzed. As a source of target cells, bone marrow macrophages (BMM phi) after 9 days of culture in hydrophobic teflon bags were used. These BMM phi were totally Ia-; however, significant Ia-expression could be induced by interferon-gamma (IFN-gamma). IFN-gamma-stimulated BMM phi, after priming with live or killed L. monocytogenes organisms were effectively lysed by the vast majority of L3T4+ T cell clones. In the absence of either IFN-gamma stimulation or antigen priming, no lysis occurred. Cytolysis was demonstrable in a conventional 4-h 51Cr-release assay and in an 18-h neutral red uptake assay and was antigen specific and class II restricted. Native T cells from L. monocytogenes-infected mice failed to lyse stimulated, L. monocytogenes-primed BMM phi and gained their cytolytic activity after antigenic restimulation in vitro. These data demonstrate that L. monocytogenes-specific L3T4+ T cells could lyse M phi presenting listerial antigens provided that Ia antigen expression had been induced. L3T4+ T cell clones produced IFN-phi after restimulation with antigen plus accessory cells in vitro and IFN-gamma secretion could be increased by costimulation with recombinant IL 2. These T cell clones conferred significant protection upon recipient mice which was more pronounced in the liver. The possible relevance of lysis by L3T4+ T cells of infected M phi to protection against and pathogenesis of intracellular bacterial infections is discussed.

Induction of Specific Cytotoxic Lymphocytes in Mice Vaccinated withBrucella abortusRB51

“…This nonspecific lysis was also shown in the 51 Cr release assay using strain 19-induced CTLs (23) and was also shown in L. monocytogenes-related CTL studies with 51 Cr release or neutral red uptake assays (18). The findings were mostly ignored due to the significant difference between nonspecific and specific CTL lyses.…”

“…Similar observations have been made for other systems. For example, it was reported elsewhere that major histocompatibility complex (MHC) class II-restricted CD4 ϩ T cells specifically lysed L. monocytogenes-infected macrophages (18) and that these killer cells belong to the Th1 subset and are capable of expressing Fas ligand (FasL) to induce apoptosis in Fas-positive target cells (14). The major target cells for these CD4…”

Specific lysis of mycobacterial antigen-bearing macrophages by class II MHC-restricted polyclonal T cell lines in healthy donors or patients with tuberculosis

“…McGregor & Forsum. 1981;Kaufmann et al, 1987). M. tuberculosis (De Libero, Flesch & Kaufmann, 1988), L. pneumophita (Blanchard ct at.. 1987), and .Salmonella typhimurium (Nencioni et at.. 1983).…”

Treating activated CD4+ T cells with either of two distinct DNA methyltransferase inhibitors, 5-azacytidine or procainamide, is sufficient to cause a lupus-like disease in syngeneic mice.

“…CD4' T cells have recently been shown to lyse stimulating MO (20,(29)(30)(31). To confirm the effect of 5-azaC, the alloreactive T cells were treated with 5-azaC and tested for syngeneic MO killing (Fig.…”