Cells that Fight Viruses May Trigger Immune Responses that Make Lupus Worse, Mouse Study Suggests

A type of immune cell that protects against viruses and cancer may worsen systemic lupus erythematosus (SLE) and trigger disease flares, a recent study with mice suggests.

Led by researchers at the U.K.’s Imperial College London, the study, “C1q restrains autoimmunity and viral infection by regulating CD8+ T cell metabolism,” appeared in the journal Science.

The development of lupus results from complex interactions between genetic and environmental factors, such as diet, tobacco smoking, medications, vitamin D deficiency, or infections.

Although alterations in two immune cell types — B-cells and CD4+ T-cells — are well-known in lupus, the role of CD8+, or cytotoxic, T-cells remains poorly understood. These cells are responsible for targeted killing of infected cells, particularly with viruses or cancer.

Previous studies have shown a strong correlation between lupus and deficiency of a molecule called C1q, a part of the complement system. This system of blood proteins is part of the body’s immune defenses, and responds to infections by initiating a series of processes at the surface of the pathogens.

Specifically, prior research showed that C1q deficiency causes ineffective clearing of dead cells. However, since multiple other molecular pathways regulate this process, scientists think an alternative function of C1q may link this molecule to autoimmunity.

Using a mouse model of lupus, the investigators found that C1q restrains the response to the body’s own tissues by regulating the energy of cytotoxic T-cells. C1q specifically targets the mitochondria — which supply power to cells — controlling the survival and function of cytotoxic T-cells.

The scientists also found that C1q deficiency leads to an abnormal T-cell response to chronic viral infections, involving autoimmunity and worsening of lupus symptoms. This could explain why lupus patients may experience a flare in symptoms when they contract a virus, the investigators hypothesized.

“These data establish a link between C1q and CD8+ T cell metabolism and may explain how C1q protects against lupus,” the scientists wrote in the study.

“I’ve been working with lupus for many years, and we’ve only recently realised these cytotoxic cells — which have such a crucial role in protecting the body against viruses, may also play a key role in the disease,” Marina Botto, the study’s senior author and a professor at Imperial College London, said in a press release.

Although its initial cause remains unknown, lupus could be sustained by viral infections that lead to an expansion of T-cells, Botto said. Of note, previous studies suggested that patients with higher levels of cytotoxic T-cells may have more severe forms of autoimmune diseases.

Botto’s team is now conducting additional research in lupus patients to gain a better understanding of how these cells may be controlled.