Th1 memory: implications for vaccine development

Authors

  • Kathryn E. Foulds,

    1. Cellular Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
    Search for more papers by this author
  • Chang-you Wu,

    1. Department of Immunology, Zhong-Shan Medical School, Guangzhou, P. R. China
    Search for more papers by this author
  • Robert A. Seder

    Corresponding author
    1. Cellular Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
      Robert A. Seder
      Cellular Immunology Section
      Vaccine Research Center
      National Institutes of Health
      40 Convent Drive, Room 3512
      Bethesda, MD 20892
      USA
      Tel.: +1 301 594 8384
      Fax: +1 301 480 2565
      E-mail: rseder@mail.nih.gov
    Search for more papers by this author

Robert A. Seder
Cellular Immunology Section
Vaccine Research Center
National Institutes of Health
40 Convent Drive, Room 3512
Bethesda, MD 20892
USA
Tel.: +1 301 594 8384
Fax: +1 301 480 2565
E-mail: rseder@mail.nih.gov

Abstract

Summary:  T-helper 1 (Th1) cells play a critical role, via interferon-γ (IFN-γ) production, in mediating intracellular killing against a variety of infectious pathogens. Thus, understanding the regulation of Th1 responses could provide better insight into vaccine design for infections requiring Th1 immunity. The cellular and molecular mechanisms that control the induction of Th1 effector cells have been well characterized. More recently, there has been substantial progress in furthering our understanding of the factors that regulate the development of Th1 memory cells. It is clear that Th1 responses are functionally heterogeneous, as defined by their ability to produce IFN-γ. Furthermore, this heterogeneity has profound implications for the capacity of distinct lineages of Th1 cells to develop into memory cells. This review emphasizes the mechanisms controlling the differentiation of naïve CD4+ T cells into effector and then memory cells in a progressive manner. It highlights the importance of IFN-γ as a positive regulator for inducing Th1 responses but a negative regulator for sustaining Th1 effector cells. In conclusion, we discuss how this current understanding of Th1 differentiation will inform vaccine design and better define immune correlates of protection.

Ancillary