Promoting wound repair

April 25, 2002

Researchers at The Scripps Research Institute (TSRI) have identified a major role in promoting wound repair played by a mysterious type of immune cell that resides mainly in the skin and gut--the gamma-delta T cell.

"Very little has been known about the function of these cells until now," says TSRI investigator Wendy Havran, Ph.D., who led the effort that detected this novel function of gamma-delta T cells.

The findings, published in the current issue of the journal Science, should be important for scientists who are interested in treating diseases that arise from epithelial cell disorders, like asthma, psoriasis, cancers, and inflammatory bowel disease.

Havran, who is an associate professor in the Department of Immunology at TSRI, has been studying gamma-delta T cells for several years. Various biological roles for the cells had been postulated by scientists, and many researchers had sought to determine how they might be involved in diseases. Until now these studies only deepened the mystery of the gamma-delta T cell.

A Cell of Known Origin but Unknown Function

What had been learned of gamma-delta T cells in the nearly two decades since their initial discovery was that they arise early in fetal development in the thymus. From there, they migrate to epithelial tissues--the thin outer layer of cells that makes up the outermost layers of skin and lines organs like the intestines and lungs.

Unlike the canonical T cells of immunology--the white blood cells--most gamma-delta T cells do not circulate through the bloodstream. Instead, they are the major T cell component of the skin, lung, and intestine, where they take up residence and monitor the neighboring epithelial cells for damage and disease.

Though gamma-delta T cells are the first T cells the thymus produces, this organ nearly shuts off production of them later in development. Throughout life, the body maintains its population of gamma-delta T cells "on-site," allowing them to divide as needed.

In the epidermis where the gamma-delta T cells are concentrated--numbering half a thousand cells per square centimeter--they have a spiny, stretched-out, finger-like shape that contacts as many skin cells as possible.

Unlike other T cells in the body, which display a wide diversity of receptors that recognize a wide diversity of antigens--the molecular components of various pathogenic invaders--the gamma-delta T cells in the skin seem to have little, if any, diversity and display a uniform receptor and recognize only a single antigen.

"When wounds heal, the epithelial cells in the skin have to proliferate and fill in the wounds," says Havran.

The new study showed that when skin is cut or damaged, keratinocytes, a type of epithelial cell common in the epidermis, release the antigen that is recognized by the gamma-delta T cells, which then become activated. Once activated, the gamma-delta T cells begin making a growth factor that binds to keratinocytes and other epithelial cells, helping them proliferate and leading to the closure of the wound.

The activated gamma-delta T cells undergo a morphological change and become little round factories, concentrating their energy on producing the growth factors and repairing the wound. They also proliferate, multiplying to increase the response to the wound.

"When gamma-delta T cells are missing, you see a delay in wound repair," says Havran, adding that the body still has other mechanisms to facilitate wound repair that eventually heal the wound.

The research article "A Role for Skin Gamma-Delta T cells in Wound Repair" is authored by Julie Jameson, Karen Ugarte, Nicole Chen, Pia Yachi, Elaine Fuchs, Richard Boismenu, and Wendy L. Havran and appears in the April 26, 2002 issue of Science.

The research was funded by the National Institutes of Health and the Leukemia and Lymphoma Society.
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Scripps Research Institute

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