Antigen-specific immune responsiveness and lymphocyte recruitment in leukocyte adhesion deficiency type II

The leukocyte adhesion deficiency syndrome type II (LAD-II) is caused by a general defect in fucose metabolism, which leads to the absence of fucosylated sugar determinants such as the selectin ligand SLe(x). In view of the important role of selectins in lymphocyte migration and homing, we have explored the in vivo immune responsiveness and lymphocyte recruitment to the skin, in response to the neo-antigen keyhole limpet hemocyanin (KLH) in a LAD-II patient. We observed a normal priming of KLH-specific T cells as well as a strong in vivo anti-KLH antibody response, both indicative of a normal T-B cell function and collaboration. Skin biopsies from the patient's skin taken prior to antigenic challenge showed the presence of normal numbers and subsets of T cells. Upon KLH injection, a large number of T cells were found to be recruited to the site of challenge, which was paralleled by up-regulation of the endothelial adhesion molecules ICAM-1 (CD54), VCAM-1 (CD106) and E-selectin (CD62E). The recruited T cell showed a normal subset distribution but lacked cutaneous lymphocyte antigen (CLA), the cutaneous homing receptor. However, the clinical symptoms of delayed-type hypersensitivity in the patient (redness and swelling) were severely depressed compared to that in the controls. In conclusion, the LAD-II patient showed a normal T cell priming and T cell-dependent antibody response, a normal baseline skin homing, and a significant T cell recruitment to the site of KLH challenge, indicating that fucosylated sugar determinants such as SLe(x) and CLA are not strictly required for adequate immune responsiveness and (skin) homing.