New technology to study T lymphocyte ageing in vitro and in vivi

Lead Research Organisation: University College London
Department Name: Immunology and Molecular Pathology

Abstract

Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.

Publications

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Agius E (2009) Decreased TNF-alpha synthesis by macrophages restricts cutaneous immunosurveillance by memory CD4+ T cells during aging. in The Journal of experimental medicine

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Akbar AN (2017) The convergence of senescence and nutrient sensing during lymphocyte ageing. in Clinical and experimental immunology

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Akbar AN (2016) Senescence of T Lymphocytes: Implications for Enhancing Human Immunity. in Trends in immunology

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Covre L (2019) Circulating Senescent T Cells Are Linked to Systemic Inflammation and Lesion Size During Human Cutaneous Leishmaniasis in Frontiers in Immunology

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Rivino L (2015) Virus-specific T lymphocytes home to the skin during natural dengue infection in Science Translational Medicine

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Seidel JA (2018) Skin resident memory CD8+ T cells are phenotypically and functionally distinct from circulating populations and lack immediate cytotoxic function. in Clinical and experimental immunology

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Shih BB (2017) Derivation of marker gene signatures from human skin and their use in the interpretation of the transcriptional changes associated with dermatological disorders. in The Journal of pathology

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Vukmanovic-Stejic M (2013) Varicella Zoster-Specific CD4+Foxp3+ T Cells Accumulate after Cutaneous Antigen Challenge in Humans in The Journal of Immunology

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Vukmanovic-Stejic M (2015) The Characterization of Varicella Zoster Virus-Specific T Cells in Skin and Blood during Aging in Journal of Investigative Dermatology

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Vukmanovic-Stejic M (2018) Enhancement of cutaneous immunity during aging by blocking p38 mitogen-activated protein (MAP) kinase-induced inflammation. in The Journal of allergy and clinical immunology

 
Title Akbar Film 
Description Video of Research Activities in The Akbar Group 
Type Of Art Film/Video/Animation 
Year Produced 2015 
Impact The film is used by the Akbar laboratory and its members when advertising our research and its impact. It has been shown at public engagement events and used when advertising new opportunities to join the group. 
URL https://youtu.be/l_426Pamxcc
 
Description The main aims of this grant were twofold. The first aim was to determine whether immune senescence could be regulated at the level of nuclear transport of key molecules from the cytoplasm to the nucleus of human T cells. The second aim of this grant was to investigate why immune responses in the skin are decreased in older individuals. In order to determine the nature of this defect, we investigated leucocyte recruitment and function in the skin



Aim 1. We found that T cell senescence was unlikely to be regulated at the nucleopore since T cells at different stages of differentiation showed the same number and distribution of these complexes. Furthermore, there were no differences in expression of neucleopores after activation of these cells. Our previous data had shown that senescent T cells had deficient transport of key signaling molecules into the nucleus of the cells and the data that was generated with the Coutavas Lab suggests that this is probably due to failure of the transport mechanisms but not the entry ports into the nucleus.



Aim2. In order to determine the nature of the defect in older individuals, we investigated leucocyte recruitment and function in the skin. Some of this data is still being analysed but the data generated thus far suggests that an essential early signal that amplify the skin response to antigen is considerably reduced in old humans. This responses revolves around the cytokine IFN-gamma, which was an unexpected finding and this work has led to a new testable hypothesis that skin resident T cells, that secrete this cytokine, are defective in old subjects.
Exploitation Route For aim 2- we have generated banks of tissue samples for microarray anlaysis which can be used to probe molecular changes during ageing and this is a resaurce that will be available to wider scientific community.
Sectors Pharmaceuticals and Medical Biotechnology
 
Description Sanofi Pasteur collaboration
Amount £15,000 (GBP)
Funding ID 11-0584-zostavax 
Organisation Sanofi Pasteur MSD 
Sector Private
Country United Kingdom
Start 02/2013 
End 02/2014
 
Description Sanofi Pasteur collaboration
Amount £15,000 (GBP)
Funding ID 11-0584-zostavax 
Organisation Sanofi Pasteur MSD 
Sector Private
Country United Kingdom
Start 02/2013 
End 02/2014
 
Description Collaboration with the Rockefeller University, to generate and analyse microarray data of normal and antigen challenged human skin from young and old individuals to investigate the mechanisms for age related changes in cutaneous immunity. 
Organisation Rockefeller University
Country United States 
Sector Academic/University 
PI Contribution This collaboration provided the expertise and the facilities to generate a unique resource: transcriptional data sets of normal and antigen challenged human skin from young and old individuals to investigate the mechanisms for age related changes in cutaneous immunity. This is a unique resource which allows us (and others) to examine age related changes at a transcriptional level in normal skin and skin challenged with recall antigen.
Collaborator Contribution This collaboration provided the expertise and the facilities to generate a unique resource: transcriptional data sets of normal and antigen challenged human skin from young and old individuals to investigate the mechanisms for age related changes in cutaneous immunity. This is a unique resource which allows us (and others) to examine age related changes at a transcriptional level in normal skin and skin challenged with recall antigen.
Impact doi: 10.1038/jid.2015.63.
Start Year 2012