Ability of γδ T cells to modulate the Foxp3 T cell response is dependent on adenosine

Whether γδ T cells inhibit or enhance the Foxp3 T cell response depends upon their activation status. The critical enhancing effector in the supernatant is adenosine. Activated γδ T cells express adenosine receptors at high levels, which enables them to deprive Foxp3+ T cells of adenosine, and to in...

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Bibliographic Details
Published in:PloS one 2018-05, Vol.13 (5), p.e0197189-e0197189
Main Authors: Liang, Dongchun, Woo, Jeong-Im, Shao, Hui, Born, Willi K, O'Brien, Rebecca L, Kaplan, Henry J, Sun, Deming
Format: Article
Language:English
Subjects:
Adenosine
Adenosine - pharmacology
Adenosine receptors
Animals
Biology and Life Sciences
Biomedical research
Bone marrow
Cell activation
Cell interactions
Cells, Cultured
Dendritic cells
Female
Forkhead Transcription Factors - genetics
Forkhead Transcription Factors - immunology
Foxp3 protein
Immunotherapy
Laboratories
Lymphocytes
Lymphocytes T
Medicine and Health Sciences
Metabolism
Mice
Mice, Knockout
Receptor, Adenosine A2A - genetics
Receptor, Adenosine A2A - immunology
Receptors
Receptors, Antigen, T-Cell, gamma-delta - genetics
Receptors, Antigen, T-Cell, gamma-delta - immunology
Research and Analysis Methods
T cell receptors
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Summary:Whether γδ T cells inhibit or enhance the Foxp3 T cell response depends upon their activation status. The critical enhancing effector in the supernatant is adenosine. Activated γδ T cells express adenosine receptors at high levels, which enables them to deprive Foxp3+ T cells of adenosine, and to inhibit their expansion. Meanwhile, cell-free supernatants of γδ T cell cultures enhance Foxp3 T cell expansion. Thus, inhibition and enhancement by γδ T cells of Foxp3 T cell response are a reflection of the balance between adenosine production and absorption by γδ T cells. Non-activated γδ T cells produce adenosine but bind little, and thus enhance the Foxp3 T cell response. Activated γδ T cells express high density of adenosine receptors and have a greatly increased ability to bind adenosine. Extracellular adenosine metabolism and expression of adenosine receptor A2ARs by γδ T cells played a major role in the outcome of γδ and Foxp3 T cell interactions. A better understanding of the functional conversion of γδ T cells could lead to γδ T cell-targeted immunotherapies for related diseases.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0197189