In 1868, the German medical student Paul Langerhans described cells in human epidermis that stained with gold chloride and exhibited prominent cell surface processes that resembled neuronal dendrites. Because of the morphologic similarities to neurons, Langerhans believed these cells consisted of primitive

Figure 1 Electron micrograph of a human Langerhans cell demonstrating the classic ultrastructural features of this cell. These include an indented nucleus, a relatively electron lucent cytoplasm, and the pathognomonic Birbeck granules (inset), which are shaped like rods or tennis racquets.

nerve tissue. Others proposed the theory that Langerhans cells represented dying melanocytes being sloughed from the skin surface. In the 1960s, the first description of the characteristic ultrastructural feature of Langerhans cells (i.e. the Birbeck granule), the observation that the tumors of histiocytosis X contained Langerhans cells, and the demonstration of normal Langerhans cells in murine skin experimentally deprived of neural crest components led to the conclusion that these cells were distinct from neurons and melanocytes. Breakthrough observations that Langerhans cells were bone marrow-derived leukocytes with potent antigen-presenting cell properties followed in the 1970s. Table 1 summarizes the historical highlights in Langerhans cell research prior to 1980. Following the correct characterization and classification of Langerhans cells, recent research has focused on the detailed cellular and molecular mechanisms involved in all aspects of Langerhans cell biology.

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