Cholera Toxin (CT), Thermolabile Enterotoxin of E. Coli (LT), its B Subunit (LTB) and LT-R192G, but not The B Subunit of CT (CTB), induce the Decrease of Resting CD4+CD25+Foxp3+ T Cells in Vitro

Author(s): Fatou Thiam, Cheikh Momar Nguer, Claire Cachia, John D. Clements, Evelyne Kohli and Christelle Basset

Previously study showed that LT-R192G, a less toxic mutant of the thermolabile enterotoxin of E. coli (LT), decreased murine regulatory CD4+CD25+Foxp3+ T cells in vitro. To go further, we tested other molecules of the cholera toxin family, i.e. native LT, the cholera toxin (CT), and their B subunits devoid of enzymatic activity, LTB and CTB. Cells from mesenteric lymph nodes of BALB/c mice were incubated with these molecules, and CD4+CD25+Foxp3+ T cells were analyzed by cytometry after two days of culture. All molecules, except CTB, decreased CD4+CD25+Foxp3+ T cells. T cell apoptosis has already been reported with these molecules, preferential effect on CD8+ T cells. So, we analyzed CD3+CD8+ and CD4+CD25+/- T cell apoptosis in the presence of LT, LT-R192G, LTB, CT and CTB in our in vitro model to detect possible preferential apoptosis of Tregs. Unexpectedly, CTB did not affect CD8+ and CD4+ T cells. Whereas LT, LT-R192G and LTB induced rapid apoptosis of CD8+ T cells with a decrease in CD3 expression, CT induced less rapid apoptosis with no decrease in CD3 expression. We observed CD4 T cell apoptosis but did not find any preferential apoptosis of CD4+CD25+ T cells (containing Foxp3+ T cells) compared with CD4+CD25- T cells. In conclusion, the enzymatic activity seems to play a significant role in apoptosis induction by CT, as CTB has no effect. In contrast, receptor binding may be essential in the observed effects for LT. Moreover, these results show the complexity and heterogeneity in the impact of these molecules.

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