Cytotoxic Immune Cells in Lips Key to Tissue Damage in Sjögren’s
In patients with severe Sjögren’s, cells build up in salivary glands
Cytotoxic CD8+ T-cells, a type of immune cells, build up in the salivary glands of the lips of patients with severe Sjögren’s syndrome, where they may kill the epithelial cells that line the glands, according to a new study.
As these cells die, the glands no longer can produce and release saliva — which suggests that cytotoxic CD8+ T-cells may be of key relevance in driving tissue damage and causing disease in Sjögren’s, the researchers noted.
“It is likely that the irreversible loss of … epithelial cells induced by activated [cytotoxic immune cells] results in the well-known secretory dysfunction of salivary … glands in this disease,” the team wrote.
The study, “Cytotoxic CD8+ T cells may be drivers of tissue destruction in Sjögren’s syndrome,” was published in the journal Scientific Reports.
Sjögren’s occurs when the body’s immune system mistakenly attacks healthy cells in the body. Because this attack usually targets cells of the glands that make saliva and tears, its main symptoms are a dry mouth and dry eyes.
While several subsets of immune T-cells have been implicated in the mechanisms underlying Sjögren’s, their exact role in the disease is still unclear.
Investigating role of immune cells
Now, a group of researchers in Japan and the U.S. measured the number of T-cells found in the salivary glands of patients with Sjögren’s.
To do this, they collected tissue samples from lip salivary glands of 13 patients with primary Sjögren’s and seven with secondary Sjögren’s. Those with secondary disease had another autoimmune disorder besides Sjögren’s.
All patients had severe disease and were not being treated.
As controls, the researchers used samples from the salivary glands located below the lower jaw of 10 patients with IgG4-related disease, and 10 individuals with chronic salivary gland inflammation, known as sialadenitis. IgG4 is an autoimmune disease that often affects the salivary glands.
Samples also were taken from the lip salivary glands of eight patients with a mucous cyst, which is a fluid-filled sac in the lips or mouth.
In patients with primary Sjögren’s, there were about twice as many T-cells as B-cells — another type of immune cells thought to be involved in Sjögren’s. For this reason, researchers continued to focus only on T-cells.
The team found that CD4+ T-cells, a type of immune cells that head the fight against infections, were present in similar amounts in samples from patients with either primary or secondary Sjögren’s.
Most of these CD4+ T-cells were Th1 cells, which help create a milieu rich in inflammatory molecules that makes cytotoxic (killer) immune cells active. In contrast, samples from patients with IgG4-related disease had a much smaller proportion of Th1 cells.
When researchers looked at the number of CD8+ T-cells in patients with primary Sjögren’s, they found that it equaled that of CD4+ T-cells. However, those with cytotoxic activity outnumbered CD4+ T-cells by about three times as much, meaning “these cells might induce the apoptotic death of specific cell types,” the researchers wrote. Apoptosis is a form of programmed cell death.
There were more dead (apoptotic) cells in tissue samples taken from patients with Sjögren’s or IgG4-related disease than in those from patients with chronic sialadenitis or a mucous cyst.
The proportion of apoptotic epithelial cells was also higher in patients with Sjögren’s than in those with IgG4-related disease. In patients with Sjögren’s, many of these apoptotic cells were acinar and ductal cells, two types of epithelial cells.
This finding was “consistent with the impaired salivary [production and release] often observed in patients with this disease,” the researchers wrote.
One way CD8+ T-cells kill other cells that are damaged or are no longer needed is by making a protein called FasL. This protein binds to another protein called Fas in target cells, triggering a series of events that lead to apoptosis.
CD8+ T-cells displaying FasL on their surface were seen to build up around and “in close proximity” to apoptotic epithelial cells rich in Fas, suggesting that cytotoxic CD8+ T-cells may kill the epithelial cells that line the salivary glands in patients with Sjögren’s.
These findings shed new light on the mechanisms underlying cytotoxic immune cells in Sjögren’s. Nonetheless, according to researchers, “the involvement of CD8+ T cells in disease initiation remains to be further explored.”