Content area
Full Text
COMMENTARY
See the related article beginning on page 537.
Nonstandard abbreviations used: cutaneous lymphocyte-associated antigen (CLA); herpes simplex virus (HSV); Epstein Barr virus (EBV); cytomegalovirus (CMV).
In mucosal immunology, the importance of homing of specific T and B lymphocyte memory cells back to their antigen's tissue of origin has long been established (1). Elucidation of the mechanisms of such homing and their role in pathogenesis and immunodeficiency may provide targets for immunotherapy or vaccines (2). Recently, there has been intense interest in lymphocyte homing during the pathogenesis of inflammatory skin diseases, particularly the role of memory T cells carrying the cutaneous lymphocyte-associated antigen (CLA) marker.
Lymphocyte homing to herpetic lesions
Antigens that precipitate inflammatory skin diseases are transported by dendritic cells to draining lymph nodes, where they encounter the full repertoire of naive T cells entering the lymph node. These T cells then proliferate and express activation molecules, including CLA, allowing them to circulate to the cutaneous site of antigen origin. In the post capillary venule, adjacent to cutaneous inflammation, CLA+ cells encounter E-selectin on the endothelial cell surface and become intermittently tethered. Then, through the upregulation of integrins such as LFA1 or VLA4 and through the interaction of these receptors with endothelial ICAM 1 and VCAM 1, respectively, the lymphocytes undergo firm adhesion and extravasate along a chemokine-- directed pathway to the exact site of inflammation (3). These processes have been well described in autoimmune or inflammatory diseases such as psoriasis and atopic dermatitis, in graft-versus-host disease and in cutaneous T cell lymphomas. It is ironic that these cutaneous homing responses, which occur in an inappropriate manner in those diseases, have not been previously investigated in the setting of local cutaneous infections, which they are well designed to control.
The results presented by Koelle et al. (4) in this issue of the JCI represent a step forward in understanding the pathogenesis of recurrent herpes simplex in particular, and of chronic or latent/reactivating cutaneous viral infections in general. After its reactivation in the neurons of the dorsal root ganglion, herpes simplex virus (HSV) is transported anterogradely to the axon terminus and is then transmitted from the axon terminus to the epidermal keratinocytes. As described...