Les auteurs de l’étude espèrent utiliser leur découverte pour développer un jour de nouvelles thérapies cellulaires.
Des processus dans le corps humain transforment des cellules immunitaires inoffensives en tueurs impitoyables.
Selon une étude récente, le corps humain a la capacité de transformer des groupes de cellules immunitaires normalement inoffensifs en tueurs impitoyables capables d’attaquer des cellules tumorales et d’autres cellules abritant des virus ou des parasites.
On pensait auparavant que les cellules T gamma delta étaient “préprogrammées” pour identifier et éliminer d’autres cellules indésirables, mais il semble maintenant que certains types de cellules ont beaucoup en commun avec des sous-ensembles “adaptatifs” bien connus de cellules T conventionnelles.
Dans une publication récente dans Cell Reports, une équipe internationale de scientifiques du Royaume-Uni, d’Australie, de Chine, des Pays-Bas et des États-Unis, dirigée par l’Université de Birmingham, a noté des parallèles frappants avec les cellules T adaptatives “tueuses” typiques.
Le coauteur principal, le professeur Ben Willcox, de l’University of Birmingham, commented: “Human gamma delta T cells have typically been assumed to be pre-programmed, however, our study shows that at least in blood, some types mirror the behavior of conventional T cells – suggesting they can be ‘trained’ to become extremely potent killers once they recognize aberrant target cells – including those infected with viruses, parasites, or possibly tumor cells.
“Our discovery has implications for efforts to develop gamma delta T cells as novel cellular therapies. We hope that it will change the way scientists think about these cells and how they might contribute to the treatment of cancer and infectious disease.”
Funded substantially by a Wellcome Trust Investigator Award, the group examined the profile of gene expression in human gamma delta T cells – showing the cells in a much more ‘adaptive’ light.
Gamma delta cells exist alongside alpha beta T cells and B cells in vertebrates. Researchers have discovered that select human gamma delta T cells appear to transform their pattern of gene expression to activate a ‘killer’ program – dependent on their exposure to abnormal target cells, with successful recognition of such targets likely a key factor triggering this transformation and subsequent attack.
An extremely strong similarity to conventional adaptive killer T cells suggests that the unique contribution of gamma delta T cells is not the type of response they ultimately mount – such as killing a target cell – but that they are able to recognize abnormal target cells in a very different way.
This suggests that they can mount unconventional adaptive responses in situations when conventional adaptive T cells cannot:
Lead author Jack McMurray, from the University of Birmingham, commented: “There are a number of scenarios in which gamma delta T cells may be uniquely suited to respond, due to their unconventional recognition capabilities. These include particular microbial, parasitic, and viral infections, and potentially some cancers.
“Our research provides a basis for ongoing studies to understand how such unconventional adaptive gamma delta T cell responses are triggered, and also for efforts to harness such responses to develop new and more effective treatments for infections and cancer.”
Reference: “Transcriptional profiling of human Vδ1 T cells reveals a pathogen-driven adaptive differentiation program” by Jack L. McMurray, Anouk von Borstel, Taher E. Taher, Eleni Syrimi, Graham S. Taylor, Maria Sharif, Jamie Rossjohn, Ester B.M. Remmerswaal, Frederike J. Bemelman, Felipe A. Vieira Braga, Xi Chen, Sarah A. Teichmann, Fiyaz Mohammed, Andrea A. Berry, Kirsten E. Lyke, Kim C. Williamson, Michael J.T. Stubbington, Martin S. Davey and Carrie R. Willcox, 24 May 2022, Cell Reports.
DOI: 10.1016/j.celrep.2022.110858
