title: Unexpected modulation of recall B and T cell responses after immunization with rotavirus-like particles in the presence of LT-R192G.
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.
authors: Laboratoire des Interactions Muqueuses-Agents transmissibles (LIMA), UPR562, UFRs Médecine et Pharmacie, IFR Santé-STIC, Université de Bourgogne, Dijon, France. thiam.fatou@hotmail.fr
authors: Fatou
authors: F
authors: Thiam
authors: Cyrille Di
authors: CD
authors: Martino
authors: Fabienne
authors: F
authors: Bon
authors: Annie
authors: A
authors: Charpilienne
authors: Claire
authors: C
authors: Cachia
authors: Didier
authors: D
authors: Poncet
authors: John D
authors: JD
authors: Clements
authors: Christelle
authors: C
authors: Basset
authors: Evelyne
authors: E
authors: Kohli
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D001427:Bacterial Toxins / Q000494:pharmacology*; D004306:Dose-Response Relationship, Immunologic; D004768:Enterotoxins / Q000494:pharmacology*; D029968:Escherichia coli Proteins / Q000494:pharmacology*; D005260:Female; D007114:Immunization; D051379:Mice; D008807:Mice, Inbred BALB C; D022243:Rotavirus Vaccines / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014771:Virion / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D001427:Bacterial Toxins; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D022243:Rotavirus Vaccines; C027538:heat-labile enterotoxin, E coli