Decoding ACD: Keratinocytes play role in all phases of allergic contact dermatitis

November 1, 2008

Allergic contact dermatitis is a cell-mediated condition in which natural killer T cells act both locally in the skin and systemically. Researchers have identified a novel transcription factor that regulates the molecule that natural killer T cells recognize when they migrate into the skin. The finding points to a new pharmacological target in the treatment of allergic contact dermatitis.

Key Points

Dr. Gaspari says his approach to a greater comprehension of contact dermatitis has begun with detecting T cells that behave differently.

"The role of conventional T cells in allergic contact dermatitis is well-established," says Dr. Gaspari, Shapiro Professor of Dermatology, department of dermatology, University of Maryland School of Medicine.

Previous studies

Previous studies of allergic contact dermatitis have emphasized the importance of conventional allergen reactive CD4+ and CD8+ T lymphocytes that recognized hapten-modified self-proteins.

While these cells are critical to allergic contact dermatitis, their frequency is very low in the cellular infiltrate of lymphocytes that migrate into the skin at hapten challenge sites, on the order of 1:10,000 to 1:100,000 frequency among infiltrating lymphocytes.

Consequently, there are major populations of lymphocytes that regularly appear in contact dermatitis that are of an antigen specificity other than that of the contact allergen.

"We have been studying allergic contact dermatitis, looking at it from a standpoint of trying to identify non-conventional T cells," Dr. Gaspari tells Dermatology Times.

"There is a certain kind of lymphocyte that migrates into the skin. We actually found that they were there," he says.

NKT cell

The type of lymphocyte, which is called a natural killer T (NKT) cell, has a T-cell antigen receptor, but it also shares receptors CD56 and CD161 and has effector functions exhibited by natural killer cells.

Previous mice studies indicated that NKT cells play a role at the systemic level in promoting hapten-specific antibodies. These antibodies circulate in the bloodstream and fix complement upon encountering hapten, which is thought to be critical in activating endothelial cells and conventional T cells to migrate into the hapten challenge sites in the skin.

In some research, it has been indicated that the cells had a systemic effect but that they did not affect the skin, according to Dr. Gaspari.

"The research demonstrated that the natural killer T cells were absolutely necessary in the sensitization phase. The NKT cells, acting at a systemic level, played a role in the sensitization process," he says.

"Recently, we demonstrated that NKT cells are acting locally and contributing to inflammation of the skin," Dr. Gaspari says, adding their role in contact dermatitis extends to acting systemically, as well as acting locally.

Novel transcription factor

Most recently, Dr. Gaspari and colleagues identified a novel transcription factor known as CEBP-beta which regulates CD1D, the molecule that NKT cells recognize when they migrate into the skin.

In a study published last June in the Journal of Investigative Dermatology, Dr. Gaspari and colleagues looked at 10 skin biopsy regimens that were taken from positive patch test reactions from 10 different patients. They identified invariant NKT cells in all specimens, with the cellular infiltrate ranging from 1.72 to 33 percent.

"They are probably present in about 1 to 5 percent," Dr. Gaspari says. "It was exceptionally high in one case."

They observed that the NKT cells were activated in all instances, expressing cytokine transcripts for IFN-gamma and IL-4. They concluded that NKT cells are continuously present during the late elicitation phase of human type IV hypersensitivity reactions.

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