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 (TH) 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 TH1-type response is really the immune system's primary defense, and whether there might be a different role for some regulatory T cells.
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We thank A. Bendelac, T. Honjo, B. Jabri, Y. Rosenberg, F. Di Rosa, R. Schwartz, N. Singh, the 'ghosts' (K. Abdi, A. Perez-Diez, A. Morgun and N. Shulzhenko) and especially P. Chappert for commenting on the manuscript. T.K. would like to express special thanks to D. Usharauli for his encouragement and support during the preparation of this Essay. We apologize to the authors whose work we didn't cite owing to lack of space. This work was supported by the intramural program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
The authors declare no competing financial interests.
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Matzinger, P., Kamala, T. Tissue-based class control: the other side of tolerance. Nat Rev Immunol 11, 221–230 (2011). https://doi.org/10.1038/nri2940
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