Targeting subset of T cells prevents, reverses MS in mice

October 07, 2019
A new study pinpoints the specific cells that cause demyelination in MS, as well as a protein on their surface that marks them. An antibody targeting the marked cells both prevented and reversed MS in a mouse model. If the findings bear out in human studies, targeting these rogue T cells could effectively treat MS, the researchers believe.

T helper cells in general have been known to drive MS, coordinating the attack on the protective myelin sheath that covers nerve fibers. Recent studies have pointed to TH17 cells. The new study by researchers at Boston Children's Hospital zeroed in on a subset of TH17-derived cells, all bearing the CXCR6 marker. These cells are fast-proliferating and very damaging, producing one set of proteins that directly damage cells and others, including GM-CSF, that stimulate an inflammatory attack by other immune cells known as macrophages.

The study showed that these cells also produce increased amounts of a protein called SerpinB1, and that this protein's presence is necessary for MS symptoms. When Sb1 was genetically deleted in T cells in the mouse MS model, fewer immune cells survived to infiltrate the spinal cord, and the disease was ameliorated as compared with control mice. The team then went on to show that these Sb1-containing cells could be readily identified with antibodies targeting the CXCR6 surface protein.

To investigate whether CXCR6-positive cells are relevant in human disease, the researchers worked with physicians in Boston Children's departments of Immunology and Neurology, as well as rheumatologists at Brigham and Women's Hospital, to obtain samples of synovial fluid from patients with inflammatory autoimmune arthritis. They found elevated levels of CXCR6+ cells in the inflamed joints. In contrast, circulating blood from the arthritis patients did not have elevated CXCR6+ cells. Nor did the blood of patients with MS or from healthy controls.

When the team used monoclonal antibodies to target CXCR6, the harmful cells largely disappeared, and mice, which were primed to get MS, did not develop the disease. Results of mouse model studies sometimes do not translate to humans and may be years away from being a marketable treatment. However, the researchers believe treatments to deplete CXCR6+ cells could mitigate MS and possibly other autoimmune disorders while largely leaving other T cell immune defenses intact.

The findings were published the journal PNAS.

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