Heterogeneity of Human CD4(+) T Cells Against Microbes

Annu Rev Immunol. 2016 May 20;34:317-34. doi: 10.1146/annurev-immunol-032414-112056.


CD4(+) T helper (Th) cells play a central role in the adaptive immune response by providing help to B cells and cytotoxic T cells and by releasing different types of cytokines in tissues to mediate protection against a wide range of pathogenic microorganisms. These functions are performed by different types of Th cells endowed with distinct migratory capacities and effector functions. Here we discuss how studies of the human T cell response to microbes have advanced our understanding of Th cell functional heterogeneity, in particular with the discovery of a distinct Th1 subset involved in the response to Mycobacteria and the characterization of two types of Th17 cells specific for extracellular bacteria or fungi. We also review new approaches to dissect at the clonal level the human CD4(+) T cell response induced by pathogens or vaccines that have revealed an unexpected degree of intraclonal diversification and propose a progressive and selective model of CD4(+) T cell differentiation.

Keywords: CD4+ Th cells; Candida; Mycobacteria; chemokine receptors; cytokines; human T cells.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity*
  • Animals
  • Bacterial Infections / immunology*
  • Biodiversity*
  • CD4 Antigens / metabolism
  • Cell Differentiation
  • Clonal Selection, Antigen-Mediated
  • Clone Cells
  • Cytotoxicity, Immunologic
  • Humans
  • Immunity, Humoral
  • Mycoses / immunology*
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / metabolism
  • Th1 Cells / immunology*
  • Th17 Cells / immunology*
  • Vaccines / immunology*


  • CD4 Antigens
  • Receptors, Antigen, T-Cell
  • Vaccines