title: Increased antigen specific T cell numbers in the absence of altered migration or division rates as a result of mucosal cholera toxin administration.
abstract: Cholera toxin (CT) is a mucosal adjuvant capable of inducing strong immune responses to co-administered antigens following oral or intranasal immunization of mice. To date, the direct effect of CT on antigen-specific CD4(+) T cell migration and proliferation profiles in vivo is not well characterized. In this study, the effect of CT on the migration pattern and proliferative responses of adoptively transferred, CD4(+) TCR transgenic T cells in orally or intranasally vaccinated mice, was analyzed by flow cytometry. GFP-expressing or CFSE-labeled OT-II lymphocytes were adoptively transferred to naïve C57BL/6 mice, and mice were subsequently vaccinated with OVA with or without CT via the oral or intranasal route. CT did not alter the migration pattern of antigen-specific T cells, regardless of the route of immunization, but increased the number of transgenic CD4(+) T cells in draining lymphoid tissue. This increase in the number of transgenic CD4(+) T cells was not due to cells undergoing more rounds of cellular division in vivo, suggesting that CT may exert an indirect adjuvant effect on CD4(+) T cells. The findings reported here suggest that CT functions as a mucosal adjuvant by increasing the number of antigen specific CD4(+) T cells independent of their migration pattern or kinetics of cellular division.
authors.affiliation: Department of Microbiology and Immunology, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Maria
authors.initials: M
authors.lastname: Kaparakis-Liaskos
authors.forename: Michelle D
authors.initials: MD
authors.lastname: Tate
authors.forename: Jason D
authors.initials: JD
authors.lastname: Price
authors.forename: Martin
authors.initials: M
authors.lastname: Pearse
authors.forename: Odilia L C
authors.initials: OL
authors.lastname: Wijburg
mesh_terms: D000281:Administration, Intranasal; D000284:Administration, Oral; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000276:immunology; D002455:Cell Division / Q000187:drug effects / Q000276:immunology*; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology*; D049109:Cell Proliferation / Q000187:drug effects; D002772:Cholera Toxin / Q000008:administration & dosage* / Q000494:pharmacology*; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects; D000939:Epitopes / Q000276:immunology*; D005070:Evans Blue / Q000378:metabolism; D005452:Fluoresceins / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D007700:Kinetics; D018655:Lymphocyte Count; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009092:Mucous Membrane / Q000187:drug effects / Q000276:immunology*; D010047:Ovalbumin / Q000276:immunology; D010455:Peptides / Q000494:pharmacology; D013388:Succinimides / Q000378:metabolism
chemical_list: C087165:5-(6)-carboxyfluorescein diacetate succinimidyl ester; D000939:Epitopes; D005452:Fluoresceins; D000949:Histocompatibility Antigens Class II; D010455:Peptides; D013388:Succinimides; D049452:Green Fluorescent Proteins; D005070:Evans Blue; D010047:Ovalbumin; D002772:Cholera Toxin
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