The sustained tissue damage in the brains and spines of people with multiple sclerosis (MS) may be caused by killer T cells misdirected by Tip-dendritic cells into adding to the formation of the inflamed lesions that characterize the disease, a study by researchers at the University of Washington found.

The study, published in Nature Immunology, concluded that the Tip dendritic cells can not only engulf oligodendrocytes or dead cells that form the myelin sheath around nerve cells, then present myelin peptides to CD4 + T cells—they can also load myelin peptides onto molecules for delivery to CD8+ T cells. The Tip dendritic cells spread the immune response from CD4+ T cells to CD8+ T cells, enabling the latter to recognize myelin protein segments from the oligodendrocytes. In effect, the CD8+ T cells respond to the oligodendrocytes by splitting them open and spilling their contents.

“Our findings are consistent with the critical role of dendritic cells in promoting inflammation in autoimmune diseases of the central nervous system,” the researchers said in a statement. The dendritic cells, they added, may possibly wait in the blood vessels of normal brain tissue to activate T-cells that have infiltrated the blood/brain barrier.

Joan Goverman, UW professor and chair of immunology, and two colleagues, Qingyong Ji and Luca Castelli, showed for the first time that naive CD8+ T cells were activated and turned into myelin-recognizing cells by special cells called Tip-dendritic cells, derived from inflammatory white blood cells that accumulate in the brain and spinal cord during experimental autoimmune encephalitis originally mediated by CD4+ T cells. Under experimental autoimmune encephalitis, the oligodendrocytes also present peptides that elicit an immune response from CD8+T cells—something that would not happen under healthy conditions.

Investigators theorized that myelin-specific CD8+T cells might contribute to the ongoing destruction of nerve-cell endings in “slow burning” MS lesions, since a drop in inflammation accompanied by an increased degeneration of axons coincided with MS leaving the relapsing-remitting stage of disease toward a more progressive state.

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