A life-changing decision

Regulator or Effector T cells: HZI researchers gain new insights into fate decision in T cells

T cells interacting with antigen presenting cells in the thymus.A proper immune response relies largely on the right balance between effector and suppressor T cells. This balance is needed to fight off pathogens while at the same time avoiding tissue damage. Researchers at the Helmholtz Centre for Infection Research (HZI) in Braunschweig have now proposed a model that explains how and when the decision which T cell takes over which function within the immune system is made. The insights published in the “Journal of Immunology” could in the long-run help to restore the immune balance in case it gets disturbed.

T cells play a crucial role in the human immune system. They orchestrate the immune response or act as killers. However, to remain functional and to prevent an over-reaction, T cells themselves need to be regulated. This role is taken over by a specific type of T cells called regulatory or suppressor T cells. “Having the right balance between T cells fighting off pathogens and those shutting down the immune response is important.  It avoids an over-reaction or over-suppression which can result in severe diseases like autoimmunity or cancer”, says PhD student Sahamoddin Khailaie, first author of the study author from the department of Systems Immunology at HZI. 

Both types of cells are differentiated from the same progenitor cells in the thymus. However, until now it is not well understood how and when the decision is made which T cell becomes an effector and which becomes a suppressor. Khailaie and his colleagues have now proposed a mathematical model that explains how progenitor cells collect information provided by the environment in the thymus and how they translate it into fate decision.

During development, thymocytes – the T cell precursor cells - express randomly generated T cell receptors that can potentially recognize any peptide, including self and foreign peptides. Whereas self peptides are those from the body in a healthy state, foreign peptides are potentially pathogenic. The progenitor cells come in contact with various antigen presenting cells showing them self-peptides, and differentiate into suppressor or effector T cells. “According to our model, collecting information from all these interactions in early development is important for progenitor cell to decide whether to become a suppressor or an effector T cell ”, says Khailaie.

Knowing according to which criterion regulatory T cells are selected and which cells are preferentially becoming suppressor cells is important because it allows scientists to develop methods to influence the selection process in the future. “We could potentially manipulate the balance between effector and suppressor cells according to our needs and by this overcome problems that result from failure in the selection process”, says Khailaie.

Original publication:

Khailaie, S., Robert, P.A., Toker, A., Huehn, J., Meyer-Hermann, M. (2014), A signal integration model of thymic selection and natural regulatory T cell commitment. J. Immunol. DOI: 10.4049/jimmunol.1400889.

The Department “Systems Immunology“ at the HZI studies mathematical modelling of immunological issues. The department is associated with the Braunschweig Integrated Centre for Systems Biology (BRICS), a new research centre for systems biology jointly founded by the HZI and the Technische Universität Braunschweig. 

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