Novel TRAIL+ NK Cell Subset May Restrain Autoreactivity in Viral Infections: Implications For Sjogren’s Disease and Virus-Induced Autoimmunity
A new study published in the journal Immunity reveals a new role of TRAIL-expressing NK cells during chronic viral infection that may provide further insights into the link between viruses and autoimmune disease development.
The TNF-related apoptosis-inducing ligand (TRAIL/Apo2L) is known to induce apoptosis and selective toxicity for cancer cells. However, TRAIL also inhibits autoimmune diseases in a number of animal models, through a variety of mechanisms ranging from inhibiting cytokine and antibody production to suppressing proliferation of autoreactive T cells (Erika Cretney et al., Immunology and Cell Biology, 2006, 84:87).
It is also known that some viral infections may contribute to autoimmune diseases but the mechanisms are poorly understood.
In the Immunity study Iona Schuster and co-workers from the University of Western Australia and the Lions Eye Institute, Nedlands, Australia report that a novel TRAIL+ NK cell subset regulates immune responses during chronic viral infection. These NK cells specifically eliminate activated CD4+ T cells in the salivary gland during chronic murine cytomegalovirus infection.
The authors make a case that in the framework of murine cytomegalovirus-induced autoimmunity, autoreactivity may be ‘constrained’ through the elimination of CD4+ T cells by TRAIL-expressing NK cells. In the absence of this activity, chronic infection was associated with a Sjogren’s-like set of symptoms in the experimental animals that had all the major features of human Sjogren’s syndrome.
The authors also suggests that the “expression of TRAIL by NK cells may serve as a general mechanism by which NK cells limit the persistence of activated cells at sites of inflammation and infection, to encourage the resolution of the response”.
Thus, from one point of view, an effector CD4+ T cell population is critical for control of chronic viral infection, but on the other, a population of NK cells acts to specifically eliminate these T cells, thereby suppressing autoimmunity.
These observations and mechanisms may have important implications for Sjogren’s syndrome or other systemic autoimmune diseases where viral etiopathogenesis might be involved.