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Unexpected Modulation of Recall B and T Cell Responses after Immunization with Rotavirus-like Particles in the Presence of LT-R192G
Laboratoire des Interactions Muqueuses-Agents transmissibles (LIMA), UPR562, UFRs Médecine et Pharmacie, IFR Santé-STIC, Université de Bourgogne, Dijon, France
Virologie Moléculaire et Structurale, UMR CNRS 2472 INRA 1157, Gif/Yvette, France
Department of Microbiology and Immunology, Tulane University Health Sciences Center, New Orleans, LA 70112, USA
These authors contributed equally to this work.
* Author to whom correspondence should be addressed.
Received: 13 July 2010 / Accepted: 3 August 2010 / Published: 5 August 2010
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: LT-R192G; Foxp3; CD25; regulatory T cells; B lymphocyte; B-1a lymphocyte; mucosal immunization; rotavirus
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Thiam, F.; Martino, C.D.; Bon, F.; Charpilienne, A.; Cachia, C.; Poncet, D.; Clements, J.D.; Basset, C.; Kohli, E. Unexpected Modulation of Recall B and T Cell Responses after Immunization with Rotavirus-like Particles in the Presence of LT-R192G. Toxins 2010, 2, 2007-2027.
Thiam F, Martino CD, Bon F, Charpilienne A, Cachia C, Poncet D, Clements JD, Basset C, Kohli E. Unexpected Modulation of Recall B and T Cell Responses after Immunization with Rotavirus-like Particles in the Presence of LT-R192G. Toxins. 2010; 2(8):2007-2027.
Thiam, Fatou; Martino, Cyrille Di; Bon, Fabienne; Charpilienne, Annie; Cachia, Claire; Poncet, Didier; Clements, John D.; Basset, Christelle; Kohli, Evelyne. 2010. "Unexpected Modulation of Recall B and T Cell Responses after Immunization with Rotavirus-like Particles in the Presence of LT-R192G." Toxins 2, no. 8: 2007-2027.