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

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 1FN-gamma producing CD4+ and CD8+ T cell and IL-10 and TGF-beta 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 106 colony forming units [CFU]/close) or high dose (14 feedings; up to 10(9) CFU/dose) or without LA feeding. Results: Low dose LA significantly promoted 1FN-gamma producing T cell responses and down-regulated Treg cell responses and their TGF-beta and IL-10 productions in all the tissues compared to the high dose IA 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-gamma 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. Conclusion: Thus the same probiotic strain in different doses can either promote or suppress IFN-gamma 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. (C) 2011 Elsevier Ltd. All rights reserved.