Unexpected Modulation of Recall B and T Cell Responses after Immunization with Rotavirus-like Particles in the Presence of LT-R192G

Toxins

Fatou Thiam²  Cyrille Di Martino²  Fabienne Bon²  Annie Charpilienne³  Claire Cachia²  Didier Poncet³  John D. Clements¹  Christelle Basset² 

[1] Department of Microbiology and Immunology, Tulane University Health Sciences Center, New Orleans, LA 70112, USA;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;

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

DOI  :  10.3390/toxins2082007

来源: mdpi

【 摘 要 】

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.

【 授权许可】

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