Tissue-based class control: the other side of tolerance

Nat Rev Immunol. 2011 Mar;11(3):221-30. doi: 10.1038/nri2940.


In this Essay, we offer a new perspective on how immune responses are regulated. We do not cover how they are turned on and off, but focus instead on the second major aspect of an immune response: the control of effector class. Although it is generally thought that the class of an immune response is tailored to fit the invading pathogen, we suggest here that it is primarily tailored to fit the tissue in which the response occurs. To this end, we cover such topics as the nature of T helper (T(H)) cell subsets (current and yet to be discovered), the nature of privileged sites, the difference between oral tolerance and oral vaccination, why the route of immunization matters, whether the T(H)1-type response is really the immune system's primary defense, and whether there might be a different role for some regulatory T cells.

Publication types

  • Research Support, N.I.H., Intramural
  • Review

MeSH terms

  • Animals
  • Antigen-Presenting Cells / immunology
  • Cytokines / physiology
  • Host-Pathogen Interactions / immunology
  • Humans
  • Hypersensitivity, Delayed / immunology
  • Immune Tolerance / immunology
  • Immunity / immunology*
  • Models, Immunological*
  • Neuroimmunomodulation
  • Organ Specificity / immunology*
  • Receptors, Immunologic / classification
  • Receptors, Immunologic / immunology
  • T-Lymphocyte Subsets / classification
  • T-Lymphocyte Subsets / immunology
  • Time Factors
  • Vaccination


  • Cytokines
  • Receptors, Immunologic