The influence of CD4+ CD25+ Foxp3+ regulatory T cells on the immune response to rotavirus infection

Bumseok Kim, Ningguo Feng, Carlos F. Narváez, Xiaosong He, Seong Kug Eo, Chae Woong Lim, Harry B. Greenberg

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

Rotavirus (RV) infection of the intestine is the major cause of severe dehydrating diarrhea in infants around the world. Although protective immunity against RV, especially acquired B and T-cell responses, has been extensively studied, our understanding of RV immunity remains incomplete. In addition, the interaction between various protective immune mechanisms in the gut and specific enteric immune suppressor systems that normally exert a regulatory function on mucosal immunity has not been extensively investigated. Among the candidate suppressor systems, we hypothesized that CD4+ CD25+ Foxp3+ regulatory T (Treg) cells may play a role in modulating RV immunity since such cells are naturally present in large numbers in the intestine and function nonspecifically. Here we demonstrate that neonatal murine RV (EC) infection induces an expansion of the Treg cell population and the magnitude of the T cell mediated immune response is modulated by Treg cells. Accordingly, when natural Treg cells in neonatal mice were depleted before virus infection, both CD4+ and CD8+ T-cell responses to RV, such as proliferation and IFN-γ secretion, were enhanced in mesenteric lymph nodes (MLNs) and the spleen. Interestingly, increased proliferation of CD19+ B cells from Treg cell depleted animals was also observed. Finally, we analyzed the in vivo effect of the Treg cell depletion on diarrheal disease, virus shedding and IgA RV-specific response. Treg cell depletion did not affect these functions. Our studies of immune modulatory Treg cells in the RV infection model may promote a better understanding of the basis for RV immunity as well as providing valuable clues for the development of more immunogenic RV vaccines.

Original languageEnglish (US)
Pages (from-to)5601-5611
Number of pages11
JournalVaccine
Volume26
Issue number44
DOIs
StatePublished - Oct 16 2008
Externally publishedYes

Keywords

  • Regulatory T cell
  • Rotavirus
  • Vaccines

ASJC Scopus subject areas

  • Immunology and Microbiology(all)
  • Infectious Diseases
  • Public Health, Environmental and Occupational Health
  • veterinary(all)
  • Molecular Medicine

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    Kim, B., Feng, N., Narváez, C. F., He, X., Eo, S. K., Lim, C. W., & Greenberg, H. B. (2008). The influence of CD4+ CD25+ Foxp3+ regulatory T cells on the immune response to rotavirus infection. Vaccine, 26(44), 5601-5611. https://doi.org/10.1016/j.vaccine.2008.07.099