Glycosphingolipids as novel targets for T-cell suppression by the B subunit of recombinant heat-labile enterotoxin. Infect Immun 1998 Apr;66(4):1299-308
Date
04/07/1998Pubmed ID
9529046Pubmed Central ID
PMC108053DOI
10.1128/IAI.66.4.1299-1308.1998Scopus ID
2-s2.0-0032036427 (requires institutional sign-in at Scopus site) 35 CitationsAbstract
Heat-labile enterotoxin subunit B (LTB) is a noncatalytic protein derived from Escherichia coli that binds to ganglioside GM1, a glycosphingolipid on the surface of mammalian cells. In this study, the effects of recombinant LTB (rLTB) on murine lymphocytes were examined in vitro. T and B cells readily bound fluorescein isothiocyanate-labeled rLTB. CD8+ T cells bound twice as much as CD4+ T cells and B cells. Exposure of T-cell subsets and B cells to rLTB abrogated mitogen-driven proliferation. CD8+ T cells were more susceptible to rLTB than either CD4+ T cells or B cells. There were differences in the sensitivity of lymphocytes from various strains of mice to rLTB. This was attributed to qualitative and quantitative differences in the CD4+ T cells. rLTB induced apoptosis in both T-cell subsets, but the level was significantly higher in CD8+ T cells. Apoptosis peaked at around 8 h after exposure to rLTB and incubation at 37 degrees C. Binding to ganglioside GM1 was essential for suppression, since rLTB/G33D, a mutant which does not bind GM1, failed to inhibit proliferation or induce apoptosis. Naive T cells, which were acutely sensitive to rLTB, became more resistant after activation. Conversely, activated T cells regained their sensitivity to rLTB when they reverted back to a resting state. A 1-h pulse with rLTB was sufficient to inhibit T-cell proliferation and cytotoxic-T-lymphocyte generation in primary mixed lymphocyte reaction cultures. CD8+ T cells were preferentially depleted in these cultures. rLTB also induced functional modifications in T cells as indicated by inhibition of gamma interferon secretion after polyclonal activation. Thus, rLTB may have immunomodulatory properties independent of its ability to induce apoptosis.
Author List
Truitt RL, Hanke C, Radke J, Mueller R, Barbieri JTAuthor
Joseph T. Barbieri PhD Professor in the Microbiology and Immunology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsApoptosis
Bacterial Toxins
Cytokines
Enterotoxins
Escherichia coli Proteins
G(M1) Ganglioside
Immunosuppressive Agents
Lymphocyte Activation
Lymphocyte Culture Test, Mixed
Mice
Mice, Inbred AKR
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Inbred DBA
Recombinant Proteins
T-Lymphocytes
