Rachael A. Clark, MD, PhD
Year elected: 2012
Current membership category: Active
Brigham and Women's Hospital
Department of Dermatology
221 Longwood Avenue
Eugene Braunwald Research Center, Rm 505A,
Boston, MA 02115
United States of America
As a dermatologist and immunologist, I have found the skin to be a valuable and accessible site in which to study human immune responses. My laboratory focuses on the study of T cells in human skin. We find that the skin of a healthy individual contains nearly 20 billion memory T cells, approximately twice as many as are present in the entire circulation. Most cutaneous effector memory T cells reside within skin under normal conditions and do not necessarily need to be recruited from circulation. Human squamous cell carcinomas exclude these skin resident T cells and human Merkel cell carcinomas suppress their activation, allowing these cancers to evade immune destruction. 30-70% of the T cells in skin are Th17 biased but most lie latent within the skin, requiring proliferation before they can produce IL-17. We find that two subtypes of cutaneous T-cell lymphoma (CTCL) arise from distinct memory T cell subsets. Mycosis fungoides (MF) arises from nonmigratory skin resident T cells and leukemic CTCL (L-CTCL) is a malignancy of migratory central memory T cells. Low dose alemtuzumab (Campath) successfully treats L-CTCL, seemingly without increasing the risk of infection. Surprisingly, alemtuzumab depleted T cells in blood but not in skin. This medication selectively depleted migratory central memory T cells, including the malignant clone, but spared a diverse population of skin resident T cells. These studies demonstrate in humans that nonmigratory skin resident T cells exist and can provide effective immune protection even in the absence of circulating T cells.
Harvard Medical School, Brigham & Women's Hospital (Primary)
Anna Greka, MD, PhD is the representative at this institution.