A new study has examined that when 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.
The study conducted at La Jolla Institute for Allergy and Immunology report that the shift is masterminded in part by NFAT, short for Nuclear Factor of Activated T cells, and best known for its crucial role in getting CD8 T cells battle-ready.
Postdoctoral researcher and co-lead author Renata M. Pereira, Ph.D., said that 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.
CD8 T cells are a subset of lymphocytes charged with killing cancer cells and cells that are infected with viruses or compromised in other ways. In previous work, the Rao and Hogan teams collaboratively pinpointed NFAT as the molecular hub that orchestrates T cell activation. When the 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 readies them to fight cancer and viral infections.
The findings are from the lab of professors Patrick Hogan and Anjana Rao, Ph.D.
Rao added that NFAT shifts the equilibrium between the activated state and exhaustion by binding to a different subset of regulatory regions within the genome.
The study is published in the journal Immunity.
