title: High dose and low dose Lactobacillus acidophilus exerted differential immune modulating effects on T cell immune responses induced by an oral human rotavirus vaccine in gnotobiotic pigs.
abstract: BACKGROUND
  Strain-specific effects of probiotics in pro- or anti-inflammatory immune responses have been well recognized. Several proinflammatory Lactobacillus strains have been shown to act as adjuvants to enhance the immunogenicity of vaccines. However, dose effects of probiotics in modulating immune responses are not clearly understood. This study examined the dose effects of Lactobacillus acidophilus (LA) NCFM strain on T cell immune responses to rotavirus vaccination in a gnotobiotic (Gn) pig model.
  
  
  METHODS
  Frequencies of IFN-γ producing CD4+ and CD8+ T cell and IL-10 and TGF-β producing CD4+CD25+ and CD4+CD25- regulatory T (Treg) cell responses were determined in the intestinal and systemic lymphoid tissues of Gn pigs vaccinated with an oral human rotavirus vaccine in conjunction with low dose (5 feedings; up to 10(6) colony forming units [CFU]/dose) or high dose (14 feedings; up to 10(9)CFU/dose) or without LA feeding.
  
  
  RESULTS
  Low dose LA significantly promoted IFN-γ producing T cell responses and down-regulated Treg cell responses and their TGF-β and IL-10 productions in all the tissues compared to the high dose LA and control groups. To the contrary, high dose LA increased the frequencies of Treg cells in most of the tissues compared to the control groups. The dose effects of LA on IFN-γ producing T cell and CD4+CD25- Treg cell immune responses were similar in the intestinal and systemic lymphoid tissues and were independent from the vaccination.
  
  
  CONCLUSIONS
  Thus the same probiotic strain in different doses can either promote or suppress IFN-γ producing T cell or Treg cell immune responses. These findings have significant implications in the use of probiotic lactobacilli as immunostimulatory versus immunoregulatory agents. Probiotics can be ineffective or even detrimental if not used at the optimal dosage for the appropriate purposes.
authors.affiliation: Department of Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Integrated Life Science Building, 1981 Kraft Dr, Blacksburg, VA 24061-0913, USA.
authors.forename: Ke
authors.initials: K
authors.lastname: Wen
authors.forename: Guohua
authors.initials: G
authors.lastname: Li
authors.forename: Tammy
authors.initials: T
authors.lastname: Bui
authors.forename: Fangning
authors.initials: F
authors.lastname: Liu
authors.forename: Yanru
authors.initials: Y
authors.lastname: Li
authors.forename: Jacob
authors.initials: J
authors.lastname: Kocher
authors.forename: Lin
authors.initials: L
authors.lastname: Lin
authors.forename: Xingdong
authors.initials: X
authors.lastname: Yang
authors.forename: Lijuan
authors.initials: L
authors.lastname: Yuan
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D015704:CD4 Antigens / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D004306:Dose-Response Relationship, Immunologic; D005856:Germ-Free Life; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000032:analysis; D007779:Lactobacillus acidophilus / Q000276:immunology*; D019936:Probiotics / Q000008:administration & dosage*; D022243:Rotavirus Vaccines / Q000008:administration & dosage / Q000276:immunology*; D013552:Swine; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014611:Vaccination / Q000379:methods*
chemical_list: D000276:Adjuvants, Immunologic; D015704:CD4 Antigens; D016827:CD8 Antigens; D053645:Interleukin-2 Receptor alpha Subunit; D022243:Rotavirus Vaccines; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D007371:Interferon-gamma