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The multi-functionality of human Vγ9Vδ2 γδ T-cells: clonal plasticity or distinct subsets?
MedLine Citation:
PMID:  22670577     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
The dominant subset of γδ T-cells in human peripheral blood expresses Vγ9 paired with Vδ2 as variable TCR elements. Vγ9Vδ2 T-cells recognize pyrophosphates derived from the microbial non-mevalonate isoprenoid biosynthesis pathway at pico- to nanomolar concentrations. Structurally related pyrophosphates are generated in eukaryotic cells through the mevalonate pathway involved in protein prenylation and cholesterol synthesis. However, micromolar concentrations of endogenous pyrophosphates are required to be recognized by Vγ9Vδ2 T-cells. Such concentrations are not produced by normal cells but can accumulate upon cellular stress and transformation. Therefore, many tumor cells are susceptible to γδ T-cell mediated lysis due to the overproduction of endogenous pyrophosphates. This explains why Vγ9Vδ2 T-cells contribute to both anti-infective and anti-tumor immunity. Ex vivo analyzed Vγ9Vδ2 T-cells can be subdivided on the basis of additional surface markers including chemokine receptors and markers for naïve and memory T-cells. At the functional level, Vγ9Vδ2 T-cells produce a broad range of cytokines, display potent cytotoxic activity, regulate αβ T-cell responses, and - quite surprisingly - can act as professional antigen-presenting cells. Thus, an exceptional range of effector functions has been assigned to a population of T-cells which all recognize invariant exogenous or endogenous pyrophosphates that are not seen by any other immune cell. Here we discuss whether this plethora of effector functions reflects the plasticity of individual Vγ9Vδ2 T-cells or can be assigned to distinct subsets.
Authors:
Dieter Kabelitz; Wei He
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-6-5
Journal Detail:
Title:  Scandinavian journal of immunology     Volume:  -     ISSN:  1365-3083     ISO Abbreviation:  -     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-6-7     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0323767     Medline TA:  Scand J Immunol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012 Blackwell Publishing Ltd.
Affiliation:
Institute of Immunology, University of Kiel, Germany Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & School of Basic Medicine, Peking Union Medical College, Beijing, China.
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