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 (BMMΦ) after 9 days of culture in hydrophobic teflon bags were used. These BMMΦ were totally Ia⁻; however, significant Ia‐expression could be induced by interferon‐γ (IFN‐γ). IFN‐γ‐stimulated BMMΦ, 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‐γ 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 BMMΦ and gained their cytolytic activity after antigenic restimulation in vitro. These data demonstrate that L. monocytogenes‐specific L3T4⁺ T cells could lyse MΦ presenting listerial antigens provided that Ia antigen expression had been induced. L3T4⁺ T cell clones produced IFN‐γ after restimulation with antigen plus accessory cells in vitro and IFN‐γ 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 MΦ to protection against and pathogenesis of intracellular bacterial infections is discussed.