The immune synapse: a mechanism for the intercellular transfer of genetic information

Nature Communications - April 19 2011

T lymphocytes transfer genetic information to antigen presenting cells via the immune synapse. This is the new finding described by the Spanish research team led by Professor Francisco Sánchez-Madrid, opening new avenues for the development of targeted therapies for the treatment of immune disorders.

To generate an immune response the T cell must be activated through direct interaction with its specific antigen. This is achieved by the formation of a highly organized structure at the contact between the T cell and an antigen-presenting cell (APC). This structure, called the immune synapse, can be likened to an embrace between the two cells. A new study by CNIC investigators shows for the first time that the immune synapse acts as an apparatus for the transfer of genetic information. This transfer is unidirectional, from the T cell to the APC, and is mediated by small vesicles called exosomes. The study was led by Doctor Sánchez-Madrid, Scientific Director of the Instituto de Investigación Sanitaria del Hospital de la Princesa (Universidad Autónoma de Madrid) and a group leader at the CNIC, working together with other CNIC groups led by Doctors Antonio Bernad and Susana González. Using advanced microscopy techniques, María Mittelbrunn, Cristina Gutiérrez-Vázquez and other members of the team demonstrated that the T cell positions its secretory apparatus at the immune synapse and releases its exosomes, which are then taken up by the APC. The genetic information contained in these vesicles is in the form of small RNA molecules called microRNAs, which are important genetic regulators that control the production of specific proteins. The study shows that microRNAs from T cell exosomes are able to regulate the expression of target genes in the recipient cell, but only when they are transferred via the immune synapse. This gene regulation influences the functioning of the recipient cell in the generation of an effective immune response. This finding increases understanding of the process of immune synapsis and identifies a previously unknown mechanism of immune regulation, confined to the microenvironment of the immune synapse. This discovery thus opens new avenues for the development of therapies to specifically modify the behavior of immune cells for the treatment of inflammatory and autoimmune disorders. The study in published in the journal Nature Communications.