The language of T lymphocytes deciphered, the Rosetta Stone of the immune system

Our immune system can defend us against aggressors so diverse (viruses, parasites, fungi and tumours) thanks to the large number of clones of T and B lymphocytes, each of which expresses a specific receptor. Until a few years ago, a "Rosetta stone", or a key for decoding this vast repertoire, was missing. Today new methods for DNA sequencing are available, but how to use sequences to trace back to the specificity of the single clones, and understand their function?

This question has now been answered by a study published on January 23rd in the prestigious journal Science and conducted by a group of researchers led by Federica Sallusto from the Institute for Research in Biomedicine (IRB). The study describes a new approach that allows deciphering the language of T lymphocytes, which are cells of the immune system that protect us from pathogens and tumours. Combining methods of Next Generation Sequencing with in vitro stimulation and analysis of specific T cells, the researchers were able for the first time to establish a complete catalogue of the immune response to pathogens and vaccines. In particular, they have catalogued all the clones that respond to a particular microorganism, determining their specificity and their functional properties, for example their ability to produce inflammatory mediators (cytokines) or to migrate to different tissues.

The research results are surprising from many points of view. First, the repertoire of specific T lymphocytes is very broad and includes thousands of clones, each characterised by a different receptor. A second unexpected result is that, within the same clone, the cells can become specialised to perform different functions and to migrate to different tissues.

According to Federica Sallusto, "using this new approach we can rapidly decipher the language of T lymphocytes, that is, their identity, specificity and function, and we can do it for the thousands of clones that mediate the immune response against microbes and vaccines. In this way we discovered that when a naive T cell recognizes a pathogen and proliferates in order to eradicate it, the progeny cells may undergo different fates, such as acquiring the ability to produce different types of cytokines or to migrate to different tissues of the organism. This extreme flexibility of T lymphocytes represents a new element that explains how the human immune system is able to respond to attacks with different weapons and on several fronts ".

For further information

Federica Sallusto
Istituto di ricerca in biomedicina (IRB)
Università della Svizzera italiana (USI)
email [email protected]
tel +41 76 326 77 34

Reference article on Science

Becattini, S., D. Latorre, F. Mele, M. Foglierini, C. De Gregorio, A. Cassotta, B. Fernandez, S. Kelderman, T.N. Schumacher, D. Corti, A. Lanzavecchia, and F. Sallusto. 2014. Functional heterogeneity of human memory CD4+ T cell clones primed by pathogens or vaccines. Science. 1260668. doi:10.1126/science.1260668.

Image

Colorized scanning electron micrograph of a T lymphocyte (credits: National Institute of Allergy and Infectious Diseases).