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In the study, Havran and Jameson compared in vivo knockout models, which lack gd T cells, to normal models. Both types of models received identical wounds to gauge the effect of the presence of the cell type on wound closure.

"When gd T cells are missing, you see a delay in wound repair," says Havran.

The skin still has the ability to close the wound eventually, though, because fibroblast cells in the connective tissue below the epidermis can step up, produce growth factor, and eventually heal the wound.

"It's a timing issue," says Jameson, who was the lead author on the latest study. "Without the gd T cells, wounds don't heal as rapidly because they don't have the rapid producers [of keratinocyte growth factor] right there."

Solving the mystery of what the gd T cells are doing has not given Havran and Jameson all the answers, however. They know that the gd T cells recognize an antigen the keratinocytes produce, but "we'd really like to know what that antigen is," says Jameson.

They would also like to elucidate the mechanism whereby the antigen is recognized and this signal is transduced within the gd T cell to initiate the morphological change that starts the production of the keratinocyte growth factor.

Havran is also interested in determining the conserved function for all epithelial resident gd T cells. She wonders whether they play roles in tissue repair in addition to producing the keratinocyte growth factor.

"Do they produce other cytokines and chemokines as well?" Havran asks.

In preliminary data, they have seen that gd T cells have the ability to recruit ab T cells and monocytes, the white blood cell precursor of the macrophage cells, which play a central role in inflammatory responses.

"We are now looking at the mechanisms of that recruitment," says Havran.

Cancer, Asthma, Psoriasis, and Ulcerative Colitis

Quite apart from the basic science, Havran and Jameson's findings should be of interest to doctors who treat diseases that arise from epithelial cell disorders. These findings may eventually lead to the discovery of chemical compounds that could be used to treat conditions like cancer, psoriasis, ulcerative colitis, and asthma. Furthermore, the models Havran and Jameson used in the current study will provide useful test beds for assaying potential compounds against these conditions.

Asthma is a chronic disease where inflammation in the lungs narrows the small airways. The Centers for Disease Control and Prevention (CDC) estimates that in the year 1998, the most recent for which data were available, some 6.8 million adults in the United States and 3.8 million American children experienced an asthma attack. The more severe among them resulted in about 2 million emergency room visits, half a million hospitilizations, and 5,438 deaths that year.

Ulcerative colitis is a painful chronic disease characterized by inflammation and ulceration of the colon and large intestine. Ulcerative colitis and a similar condition known as Crohn's Disease afflict about one million Americans.

Psoriasis is a chronic disease of the skin that afflicts an estimated two percent of the population. Though generally quite mild, it can cause a great deal of discomfort in those who suffer from it.

Havran and Jameson's findings may be relevant to certain types of cancer because gd T cells are cytotoxic and have the ability to kill tumor cells.

Knowing the role of these cells in the skin and the mechanism whereby they interact with other skin cells may yield potential targets for intervention in all of these conditions. For instance, there is a correlation between asthma and the number of gd T cells in the lungs. During an attack, the number of gd T cells is elevated, which may be the body's attempt to deal with the problem.

Treatments that are based on a thorough understanding of the underlying mechanisms of gd T cells may prove to be better than currently existing therapy. Current treatments for asthma, ulcerative colitis, and psoriasis include anti-inflammatories like aspirin and corticosteroids, which shut down the response of the ab T cells. Havran suspects that this sort of treatment is sub-optimal because it also kills the gd T cells.

"These gd T cells are also important for tissue repair," she says. "We think the steroids delay tissue repair by killing off the gd T cells.

"We hope that this [work] will lead to new therapeutic agents that spare the gd T cells," says Havran.


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Dendritic epidermal T cells (red) interact with neighboring keratinocytes (blue). The dendritic morphology of the gd T cells allows for intimate contact between these resident skin cells. Epidermal tissue was stained with DAPI and a gd T cell receptor-specific antibody.