Activating and immunoregulatory signal networks in T cells
Prof. Kjetil Tasken
Centre for Molecular Medicine Norway, Nordic EMBL Partnership and Biotechnology Centre, University of Oslo, Norway
Analyses of signaling events by classical biochemical approaches typically represent averaged readouts within cell populations, which is a restriction when addressing signaling in mixed cell populations. By combining flow cytometry with a panel of phosphospecific antibodies against several signal molecules in a multi-parameter analysis it is possible to obtain a higher level of understanding of the signal transduction dynamics at a single cell level. Furthermore, the fluorescent cell bar coding technique allows pooling of samples for concomitant analysis with the same base line.
Regulatory T cells (Tregs) constitute a T cell subpopulation with suppressive properties. Peripherally induced Tregs occur at sites of antigenic activation and modulate immune responses to avoid tissue damage and inflammation. In chronic infections and cancer, Treg-mediated immunosuppression is dysfunctional and inhibits clearance of infections or targeting of cancer cells by the immune system. Furthermore, Tregs need to be activated in order to be fully suppressive. Activated Tregs have been shown to be down-regulated in autoimmune diseases and upregulated in chronic inflammation. Hence, control of Treg activation could offer clinical benefit. Peripherally induced regulatory T cells and other inflammatory class also express COX-2, secrete prostaglandin E2 (PGE2) and elicit an immunosuppressive cAMP signaling pathway that we have mapped out in effector T cells which can be targeted in clinical settings.