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The role of cytokines in determining the Th1/Th2 phenotype of an immune response: Coherence of the T cell response and the Cytokine Implementation Hypothesis
The widely accepted Cytokine Milieu Hypothesis proposes that the cytokine milieu, in which antigen activates CD4 T cells, from a non‐T cell source, primarily determines the Th subset to which the ensuing effector Th cells belong. We focus on the generation of Th1 and Th2 cells. We briefly restate th...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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John Wiley and Sons Inc.
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9286540/ http://dx.doi.org/10.1111/sji.13110 |
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author | Bretscher, Peter A. |
author_facet | Bretscher, Peter A. |
author_sort | Bretscher, Peter A. |
collection | PubMed |
description | The widely accepted Cytokine Milieu Hypothesis proposes that the cytokine milieu, in which antigen activates CD4 T cells, from a non‐T cell source, primarily determines the Th subset to which the ensuing effector Th cells belong. We focus on the generation of Th1 and Th2 cells. We briefly restate the grounds for the Threshold Hypothesis we favour for how the Th1/Th2 phenotype of a response is primarily determined: tentative and robust thresholds of antigen‐mediated CD4 T cell interactions lead to the generation of Th1 and Th2 cells. The component antigens of pathogens are present in different amounts. It is expected, within the context of the threshold mechanism that, although there is often an initial predominance of Th1 or Th2 cells, some Th cells of the opposing type are initially generated. An initially somewhat heterogeneous Th response is known to become with time more ‘coherent’ in its Th1/Th2 phenotype. I propose The Cytokine Implementation Hypothesis as a mechanism for how coherence is achieved. Most cytokines made by Th cells of one subset tend to facilitate the further generation of Th cells of this subset and/or inhibit the generation of Th cells of opposing subsets, accounting for how coherence may be achieved. Many observations on which The Cytokine Milieu Hypothesis is based are accounted for by this alternative hypothesis. We outline predictions of the new hypothesis and discuss the importance of coherence of immune responses for their efficacy in protecting against foreign invaders. |
format | Online Article Text |
id | pubmed-9286540 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-92865402022-07-19 The role of cytokines in determining the Th1/Th2 phenotype of an immune response: Coherence of the T cell response and the Cytokine Implementation Hypothesis Bretscher, Peter A. Scand J Immunol Discussion Forum The widely accepted Cytokine Milieu Hypothesis proposes that the cytokine milieu, in which antigen activates CD4 T cells, from a non‐T cell source, primarily determines the Th subset to which the ensuing effector Th cells belong. We focus on the generation of Th1 and Th2 cells. We briefly restate the grounds for the Threshold Hypothesis we favour for how the Th1/Th2 phenotype of a response is primarily determined: tentative and robust thresholds of antigen‐mediated CD4 T cell interactions lead to the generation of Th1 and Th2 cells. The component antigens of pathogens are present in different amounts. It is expected, within the context of the threshold mechanism that, although there is often an initial predominance of Th1 or Th2 cells, some Th cells of the opposing type are initially generated. An initially somewhat heterogeneous Th response is known to become with time more ‘coherent’ in its Th1/Th2 phenotype. I propose The Cytokine Implementation Hypothesis as a mechanism for how coherence is achieved. Most cytokines made by Th cells of one subset tend to facilitate the further generation of Th cells of this subset and/or inhibit the generation of Th cells of opposing subsets, accounting for how coherence may be achieved. Many observations on which The Cytokine Milieu Hypothesis is based are accounted for by this alternative hypothesis. We outline predictions of the new hypothesis and discuss the importance of coherence of immune responses for their efficacy in protecting against foreign invaders. John Wiley and Sons Inc. 2021-10-29 2022-01 /pmc/articles/PMC9286540/ http://dx.doi.org/10.1111/sji.13110 Text en © 2021 The Authors. Scandinavian Journal of Immunology published by John Wiley & Sons Ltd on behalf of The Scandinavian Foundation for Immunology. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
spellingShingle | Discussion Forum Bretscher, Peter A. The role of cytokines in determining the Th1/Th2 phenotype of an immune response: Coherence of the T cell response and the Cytokine Implementation Hypothesis |
title | The role of cytokines in determining the Th1/Th2 phenotype of an immune response: Coherence of the T cell response and the Cytokine Implementation Hypothesis |
title_full | The role of cytokines in determining the Th1/Th2 phenotype of an immune response: Coherence of the T cell response and the Cytokine Implementation Hypothesis |
title_fullStr | The role of cytokines in determining the Th1/Th2 phenotype of an immune response: Coherence of the T cell response and the Cytokine Implementation Hypothesis |
title_full_unstemmed | The role of cytokines in determining the Th1/Th2 phenotype of an immune response: Coherence of the T cell response and the Cytokine Implementation Hypothesis |
title_short | The role of cytokines in determining the Th1/Th2 phenotype of an immune response: Coherence of the T cell response and the Cytokine Implementation Hypothesis |
title_sort | role of cytokines in determining the th1/th2 phenotype of an immune response: coherence of the t cell response and the cytokine implementation hypothesis |
topic | Discussion Forum |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9286540/ http://dx.doi.org/10.1111/sji.13110 |
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