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Toxins (Basel). 2010 Aug;2(8):2007-27. doi: 10.3390/toxins2082007. Epub 2010 Aug 5.

Unexpected modulation of recall B and T cell responses after immunization with rotavirus-like particles in the presence of LT-R192G.

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1
Laboratoire des Interactions Muqueuses-Agents transmissibles (LIMA), UPR562, UFRs Médecine et Pharmacie, IFR Santé-STIC, Université de Bourgogne, Dijon, France. thiam.fatou@hotmail.fr

Abstract

LT-R192G, a mutant of the thermolabile enterotoxin of E. coli, is a potent adjuvant of immunization. Immune responses are generally analyzed at the end of protocols including at least 2 administrations, but rarely after a prime. To investigate this point, we compared B and T cell responses in mice after one and two intrarectal immunizations with 2/6 rotavirus-like particles (2/6-VLP) and LT-R192G. After a boost, we found, an unexpected lower B cell expansion measured by flow cytometry, despite a secondary antibody response. We then analyzed CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs) and CD4(+)CD25(+)Foxp3(-) helper T cells after in vitro (re)stimulation of mesenteric lymph node cells with the antigen (2/6-VLP), the adjuvant (LT-R192G) or both. 2/6-VLP did not activate CD4(+)CD25(+)Foxp3(-) nor Foxp3(+) T cells from non-immunized and 2/6-VLP immunized mice, whereas they did activate both subsets from mice immunized with 2/6-VLP in the presence of adjuvant. LT-R192G dramatically decreased CD4(+)CD25(+)Foxp3(+) T cells from non-immunized and 2/6-VLP immunized mice but not from mice immunized with 2/6-VLP and adjuvant. Moreover, in this case, LT-R192G increased Foxp3 expression on CD4(+)CD25(+)Foxp3(+) cells, suggesting specific Treg activation during the recall. Finally, when both 2/6-VLP and LT-R192G were used for restimulation, LT-R192G clearly suppressed both 2/6-VLP-specific CD4(+)CD25(+)Foxp3(-) and Foxp3(+) T cells. All together, these results suggest that LT-R192G exerts different effects on CD4(+)CD25(+)Foxp3(+) T cells, depending on a first or a second contact. The unexpected immunomodulation observed during the recall should be considered in designing vaccination protocols.

KEYWORDS:

B lymphocyte; B-1a lymphocyte; CD25; Foxp3; LT-R192G; mucosal immunization; regulatory T cells; rotavirus

PMID:
22069670
PMCID:
PMC3153289
DOI:
10.3390/toxins2082007
[Indexed for MEDLINE]
Free PMC Article
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