Expression Of Cutaneous Lymphocyte-associated Antigen Research Articles

Bacterial superantigens induce T cell expression of the skin-selective homing receptor, the cutaneous lymphocyte-associated antigen, via stimulation of interleukin 12 production.

T lymphocyte infiltration is a prominent feature of the skin inflammation associated with infections by toxin (superantigen)-secreting Staphylococcus aureus or Streptococcus bacteria. The cutaneous lymphocyte-associated antigen (CLA) has been hypothesized to be a homing receptor (HR) involved in selective migration of memory/effector T cells to the skin. Since the expression of this putative skin-selective HR is known to be under strict microenvironmental control, we sought to determine the effect of staphylococcal and streptococcal toxins on T cell expression of CLA. After in vitro stimulation of peripheral blood mononuclear cells with staphylococcal enterotoxin B, toxic shock syndrome toxin-1, and streptococcal pyrogenic exotoxins A and C, there was a significant increase in the numbers of CLA+ T cell blasts (p < 0.01), but not blasts bearing the mucosa-associated adhesion molecule alpha e beta 7-integrin, compared with T cells stimulated with phytohemaglutinin (PHA) or anti-CD3. Bacterial toxins were also found to specifically induce interleukin (IL) 12 production. More importantly, induction of toxin-induced CLA expression was blocked by anti-IL-12, and the addition of IL-12 to PHA-stimulated T cells induced CLA, but not alpha e beta 7-integrin, expression. These data suggest that bacterial toxins induce the expansion of skin-homing CLA+ T cells in an IL-12-dependent manner, and thus may contribute to the development of skin rashes in superantigen-mediated diseases.

Skin-homing T lymphocytes: detection of cutaneous lymphocyte-associated antigen (CLA) by HECA-452 in normal human skin.

The immigration of circulating T cells into specific tissues is directed by the interaction between adhesion molecules on lymphocyte subpopulations and their ligands on vascular endothelium. Of these, endothelial leucocyte adhesion molecule (ELAM-1), weakly expressed in normal human skin (NHS), seems to be the counter-structure for cutaneous lymphocyte-associated antigen (CLA). CLA is a 200 kDa cell-surface glycoprotein of which the sugar moieties sialyl Le(a) and sialyl Le(x) are the possible epitopes recognized by the monoclonal antibody HECA-452. HECA-452 was originally described as a marker for lymphoid organ high endothelial cells, but 16% of peripheral-blood-derived T cells react with this antibody. We studied the expression of CLA on the cellular constituents of the skin immune system (SIS). By applying immunohistochemical double staining, 41% of CD3+ T cells, 44% of CD4+ T cells and 31% of CD8+ T cells were found to express CLA. Keratinocytes, CD1a+ Langerhans cells (LC) and endothelial cells did not express HECA-452 in significant numbers in NHS. Monocytes were found to express HECA-452 in 14% of CD68+ cells. CLA expression was present on a relatively low percentage of T cells and subsets localized distant from NHS vessels, suggesting loss of the molecule during further migration after transendothelial passage. However, intraepidermal T cells expressed CLA in similar percentages to T cells localized directly perivascularly. Our findings support the notion that CLA expression by T cells is associated with their homing into cutaneous structures.