HECA-452+ T Cells Migrate Through Superficial Vascular Plexus but Not Through Deep Vascular Plexus Endothelium

Abstract

The skin is nourished by two interconnected vascular systems, the superficial vascular plexus coursing just beneath the epidermis and the deep vascular plexus located above the subcutaneous tissue. Skin inflammatory T cells in diseases, such as psoriasis or dermatitis, strikingly aim for the superficial vascular plexus without involving the deep vascular plexus, and the infiltrating T cells bear a distinct phenotype expressing the cutaneous lymphocyte-associated antigen, which is recognized by mAb HECA-452. We wanted to know whether HECA-452+ lymphocytes indeed are able to distinguish between superficial and deep vascular plexus homing sites. Employing the hu-SCID mouse model grafted with human skin and human T cells, as described previously, we developed a new skin-grafting strategy providing superficial and deep vascular plexus skin specimens placed separately onto the same mouse. Fourteen days after allogeneic human T cell grafting, both human skin sites were densely infiltrated by human T cells, but only T cells within the superficial vascular plexus, but not within the deep vascular plexus, expressed the cutaneous lymphocyte-associated antigen. IL-2 and IFN-gamma expression and allogeneic vessel destruction were present within both superficial and deep vascular plexus skin. This model provides direct evidence that expression of a specific homing receptor is indeed able to direct lymphocyte traffic, not only to a distinct organ but also to a distinct vascular bed within one organ.