CD8 T Cells Sometimes Lose Its Ability to Effectively Fight Infections

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."

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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.

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