Until now very little has been known about the function of these cells, according to TSRI investigator Wendy Havran, who led the effort that detected this novel function of gamma-delta T cells.
The findings, published in 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.
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 neighbouring 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 centimetre - 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 recognise 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 recognise only a single antigen.
Havran explains that when wounds heal, the epithelial cells in the skin have to proliferate and fill in the wounds.
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 recognised 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.
If gamma-delta T cells are absent there is a delay in wound repair, although the body has other mechanisms it can use to facilitate wound repair.
The research article, entitled ‘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 appeared 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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Science Daily
30 April 2002
