No abstract

Natural killer T (NKT) cells are CD1d-restricted lymphoid cells and are characterized by an invariant T-cell receptor, which in humans consists of a Va24 chain paired with a Vb11 chain. These cells are known for their rapid production of large amounts of cytokines (e.g., Vb11+ NKT cell numbers in both healthy controls and cancer patients and demonstrate that in both groups females have higher NKT cell levels compared to males. In a large group of 120 cancer patients, we show that circulating Va24+ NKT cell numbers are about 50% lower than in ageand gender-matched healthy controls and that this decrease is independent of tumor type or tumor load. This decrease was not restored upon tumor removal by means of surgery or radiotherapy. Even though the percentage of NKT cells that secrete IFN-g, as detected by ELISPOT, is normal in cancer patients, the absolute number of circulating IFN-g-secreting NKT cells is reduced. Together, our results suggest that the reduced circulating Va24 + Vb11+ NKT cell numbers in cancer patients are not affected by tumor load, but might actually reflect a risk factor for tumor development, e.g., by hampering efficient tumor immunosurveillance. ' 2005 Wiley-Liss, Inc.

No abstract

No abstract

Ultraviolet B radiation can suppress cellular immunity. One of the mechanisms related to this immunosuppression is the disappearance of Langerhans cells from the epidermis. The aim of this study was to establish the mechanism of ultraviolet B-induced Langerhans cell disappearance in healthy individuals. The two most likely mechanisms for Langerhans cell disappearance are apoptosis and migration. Apoptosis was assessed in vivo by exposing buttock skin of 10 healthy volunteers to six minimal erythema doses of ultraviolet B. Only very few apoptotic Langerhans cells could be observed in sections from the ultraviolet B-exposed skin. Migration of Langerhans cells cannot be established in skin sections and suction blisters were therefore raised in an attempt to trap migrating Langerhans cells in the sub-basal membrane blister fluid. Blisters were raised on the flexor side of the lower arm of 30 healthy volunteers at several time points after exposure of the skin to six minimal erythema doses of ultraviolet B. Blister fluid was collected and blister roofs were removed to check for Langerhans cell disappearance. Langerhans cells were detected in the blister fluid of the ultraviolet B-exposed skin and not of the unexposed skin. The number of Langerhans cells in the blister fluid peaked at about 18 h after ultraviolet exposure, which coincided with the largest depletion of Langerhans cells in the blister roof. A fraction (20-30%) of the Langerhans cells in the blister fluid stained positive for DNA damage (cyclobutyl pyrimidine dimers), showing that they originated from the epidermis. Ultraviolet B-induced Langerhans cell disappearance appears to be mainly attributable to migration.