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Cell clustering and delay/arrest in T-cell division implicate a novel mechanism of immune modulation by E. coli heat-labile enterotoxin B-subunits. - PubMed - NCBI
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Cell Immunol. 2015 Jun;295(2):150-62. doi: 10.1016/j.cellimm.2015.02.014. Epub 2015 Mar 5.

Cell clustering and delay/arrest in T-cell division implicate a novel mechanism of immune modulation by E. coli heat-labile enterotoxin B-subunits.

Author information

1
College of Veterinary Medicine, Nursing & Allied Health, Department of Pathobiology, Tuskegee University, 1200 Montgomery Road, Tuskegee, AL 36088, USA; Kafrelshikh University, College of Veterinary Medicine, Kafrelsheikh, Egypt.
2
College of Veterinary Medicine, Nursing & Allied Health, Department of Pathobiology, Tuskegee University, 1200 Montgomery Road, Tuskegee, AL 36088, USA; Middle Technical University, Institute of Medical Technology, Department of Community Health, Baghdad, Iraq.
3
College of Veterinary Medicine, Nursing & Allied Health, Department of Pathobiology, Tuskegee University, 1200 Montgomery Road, Tuskegee, AL 36088, USA.
4
Pennsylvania School of Dental Medicine, Department of Microbiology, Philadelphia, PA 19104, USA.
5
The Department of Microbiology & Immunology and The Witebsky Center for Microbial Pathogenesis and Immunology, School of Medicine and Biomedical Sciences, 138 Farber Hall, 3435 Main St., University at Buffalo, NY 14214, USA.
6
College of Veterinary Medicine, Nursing & Allied Health, Department of Pathobiology, Tuskegee University, 1200 Montgomery Road, Tuskegee, AL 36088, USA. Electronic address: tnashar@mytu.tuskegee.edu.

Abstract

The B-subunits of heat-labile enterotoxins LT-I (LT-IB) and LT-IIa (LT-IIaB) are strong adjuvants that bind to cell-surface receptors, including gangliosides G(M1) and GD1b, respectively. LT-IIaB also binds TLR-2. We demonstrate for the first time that co-incubation with the B-subunits induces significant clustering of B cells after only 4h, and B and T cells in 24h. Clustering was dependent on intact B-subunits, but not on the TLR-2 binding activity of LT-IIaB, indicating it was ganglioside-mediated. Treatment of B cells with LT-IB, a mixture of LT-IB+LT-IIaB, but not LT-IIaB alone, caused a delay in T cell division following ovalbumin endocytosis. B cell receptor-mediated uptake in presence of each treatment caused an arrest, but with increased production of IL-2. Further, treatments differentially increased the proportion of macrophages expressing MHC class-II. These results highlight the outcomes of interplay between signals involving different receptors and implicate a novel mechanism of adjuvanticity.

KEYWORDS:

Adjuvant; B cells; Enterotoxins; GD1; GM1; Gangliosides; T cells; TLR-2; Vaccine

PMID:
25880107
PMCID:
PMC4439354
DOI:
10.1016/j.cellimm.2015.02.014
[Indexed for MEDLINE]
Free PMC Article
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