While fighting chronic viral infections or cancers, a key division of the immune system, known as CD8 T cells, sometimes loses its ability to effectively fight foreign invaders, revealed a study conducted at La Jolla Institute for Allergy and Immunology.
Postdoctoral researcher and co-lead author Renata M. Pereira, Ph.D., said, "Understanding the molecular mechanism that leads to CD8 T cell exhaustion brings them a step closer to developing strategies to induce optimal T cell responses that can successfully clear infections and kill tumor cells and conversely, it may allow them to interfere with autoimmune responses that paradoxically depend on the same protein."
Previous studies by the research team has pinpointed NFAT (Nuclear Factor of Activated T cells) as the molecular hub that orchestrates T cell activation. When this T cell receptor on the surface of CD8 T cells recognizes a foreign protein, it kicks off a signaling cascade that culminates in the activation of NFAT and its partner AP-1. Together, the pair binds to regulatory regions in the genome and initiates a genetic program that activates T cells and gets them ready to fight cancer and viral infections.
Researcher Rao said, "NFAT shifts the equilibrium between the activated state and exhaustion by binding to a different subset of regulatory regions within the genome."
The study appears in the journal Immunity.