Regulatory T (T reg) cells calm the immune system and thwart attacks on the body's own tissues. On page 793 Dai et al. report that another T cell type performs a similar job and might serve as a backup to impaired T reg cells in autoimmune diseases. The cells could provide a new way to treat diseases such as lupus.
The researchers were investigating a puzzling variety of CD4+ T cells that carries the NKG2D receptor. Previous studies on the cells’ functions had given ambiguous results. They seem to protect tumors by quashing immune attacks. In rheumatoid arthritis and Crohn's disease, however, expansions of NKG2D+CD4+ T cells correlate with disease severity, hinting that the cells promote autoimmunity.
Dai et al. straightened out the confusion by showing that the NKG2D-carrying CD4+ T cells normally serve as immune system regulators. These cells recognize self antigens but ignore antigens from pathogens, suggesting that they aren't taking part in antimicrobial defense. They also release an immune-soothing combination of cytokines, including interleukin-10 and TGF-β. This cytokine profile differentiates the cells from other CD4+ T cells that switch on NKG2D only during inflammation and emit pro-inflammatory cytokines such as interferon-γ and TNF-α.
To determine whether these regulators affect autoimmune disease, the team tested blood samples from patients with the juvenile-onset form of lupus, which waxes and wanes in severity. During disease flare-ups, the team discovered, NKG2D+CD4+ T cell numbers plunge, and their abundance rises again during remissions.
Although the cells cannot prevent lupus flare-ups, they seem to alleviate the attacks. T reg cells often malfunction in the disease, but the NKG2D-carrying CD4 T+ cells appear to remain healthy, suggesting that infusions of the cells might quell autoimmune symptoms.
