Analysis of cell-mediated immune parameters in dextran sulfate pretreated BALB/c mice after immunization with heat-killed Listeria monocytogenes

Abstract

Protective immunity against infection by Listeria monocytogenes is best induced by live, virulent organisms. Heat-killed organisms or antigenic fractions by themselves cannot induce active protection, however, in combination with proper adjuvants, protection can be demonstrated. This study investigated the ability of dextran sulfate 500 (DS) in combination with heat-killed Listeria monocytogenes (HKLM) to induce immunity. Pretreatment of mice with a 30 mg/kg dose of DS followed one day later by 1 x 10^9 HKLM allowed generation of specific immunity. Mice treated in such a manner survived challenge with a 50 LD50 dose of L. monocytogenes. This protection was not as effective as that induced by immunization with live, virulent L. monocytogenes. Although delayed type hypersensitivity (DTH) was not detected directly, passive transfer of splenic T lymphocytes indicated that the protection was of a cellular nature. The mechanism of action of DS was assessed in two ways. First, the effect of DS on antigen uptake showed that there was no change in the site of deposition. Second, using mitogen analysis, it was shown that DS significantly enhanced the response of splenic lymphocytes to concanavalin A (Con-A), but not to phytohemagglutinin (PHA), nor lipopolysaccharide (LPS). It was found that the enhancement of the Con-A response was dependent upon macrophages (MΦ). DS induces IL-1 synthesis in MΦ, and in response with other stimuli, increased secretion of IL-1 was noted. The level of secreted IL-2 from stimulated whole splenic cells was decreased when compared to that from normal mice. These data suggest that pretreatment of mice with DS allows the MΦ to potentiate helper T cell replication by the production of IL-1.