An Antimicrobial Activity of Cytolytic T Cells Mediated by Granulysin

Abstract

Cytolytic T lymphocytes (CTLs) kill intracellular pathogens by a granule-dependent mechanism. Granulysin, a protein found in granules of CTLs, reduced the viability of a broad spectrum of pathogenic bacteria, fungi, and parasites in vitro. Granulysin directly killed extracellular Mycobacterium tuberculosis, altering the membrane integrity of the bacillus, and, in combination with perforin, decreased the viability of intracellular M. tuberculosis. The ability of CTLs to kill intracellular M. tuberculosis was dependent on the presence of granulysin in cytotoxic granules, defining a mechanism by which T cells directly contribute to immunity against intracellular pathogens.

In vivo rejection of tumor cells dependent on CD8 cells that kill independently of perforin and FasL

“…Therefore, we can hypothesize that B7-1 costimulation on the cells could indirectly amplify CTL lytic functions by producing sufficient amount of various cytokines that can upregulate expression of cytolytic molecules on the effectors. It has been reported that other cytotoxic molecules that are constituted in a granule, for example granulysin, 41 can be involved in the perforin-independent CTL killing. 42 Moreover, since granzyme B can directly enter target cells by a receptor, without the involvement of perforin, the cells can be induced to undergo apoptosis by both perforin-and FasL-independent pathways.…”

NK-lysin of channel catfish: Gene triplication, sequence variation, and expression analysis

“…In recent years, extensive research has been conducted for the analysis of structure and antimicrobial activities of NK-lysin (Stenger et al, 1998;Ernst et al, 2000;Gansert et al, 2003;Jacobs et al, 2003). NK-lysin genes share sequence similarities to the poreforming proteins of Entamoeba histolytica, termed amoebapores (Leippe, 1995).…”

“…NK-lysin genes share sequence similarities to the poreforming proteins of Entamoeba histolytica, termed amoebapores (Leippe, 1995). They have been reported to have antimicrobial activities against a wide spectrum of microorganisms including bacteria, fungi, protozoa, and parasites (Stenger et al, 1998;Ernst et al, 2000;Gansert et al, 2003;Jacobs et al, 2003), and therefore, have been widely regarded as antimicrobial peptides. In contrast to classical antibiotics, these peptides act by direct physical destabilization of the target cell membrane with a high specificity for bacteria (Schroder-Borm et al, 2003).…”

Therapeutic effect of DNA vaccines combined with chemotherapy in a latent infection model after aerosol infection of mice with Mycobacterium tuberculosis

“…12 These cellular immune responses also appear to be required for maximally effective antituberculosis immunity in humans. 13,14 Recent understanding of the immunopathogenesis of TB suggests the possible application of adjunctive immunotherapy for TB treatment. Accordingly, DNA vaccination has been actively pursued, since it is known to establish cellular immune responses, including cytotoxic T-lymphocyte (CTL) and Th1 responses.…”