Mature T cells throw out tube-like protrusions to avoid being swept away by blood rushing by at high speed. As they gently roll along, tether after tether is peeled loose and slung forward like a lasso to gain new traction.Credit: Michael Abadier, Ph.D., La Jolla Institute for Allergy and Immunology
To eradicate pathogens or counteract inflammation, cells of the immune system move through often rapid blood flow toward peripheral disease sites, such as skin, gut or lung. Thus a goal of immunologists has been to define the repertoire of molecules that not only keep fast-moving immune cells on course but allow them to access inflamed tissues.
Now, a team led by La Jolla Institute for Allergy and Immunology (LJI) researcher Klaus Ley, M.D., reports that helper T cells move toward inflamed tissue using membrane protrusions that stabilize them and provide traction on the vasculature. Using high-resolution microscopy and global molecular analysis, the team shows that immature T cells lack these protrusions but that maturing T-cells switch on a gene expression program to create material to construct them.
That work, published in the Dec. 26. , 2017, issue of Cell Reports, provides a brand new collection of factors potentially useful to modulate immune responses in conditions as diverse as cancer and autoimmune disease.
“Immature T cells remain in lymphoid organs and can’t move into sites of infection,” says Ley, a professor and head of in LJI’s Division of Inflammation Biology. “To reach their targets, T cells must first acquire biomechanical properties necessary for migratory behavior. We now know they do that in part by deploying strategies similar to those we previously discovered in cells called neutrophils.”
Michael Abadier, Akula Bala Pramod, Sara McArdle, Alex Marki, Zhichao Fan, Edgar Gutierrez, Alex Groisman, Klaus Ley. Effector and Regulatory T Cells Roll at High Shear Stress by Inducible Tether and Sling Formation. Cell Reports, 2017; 21 (13): 3885 DOI: 10.1016/j.celrep.2017.11.099
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