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

Abstract

SummaryT 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-l, 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 c~eB7-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 ote/~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.

CD2‐mediated stimulation of the naive CD4+ T‐cell subset promotes the development of skin‐associated cutaneous lymphocyte antigen‐positive memory cells

“…APC). In addition, we tested IL-12 as a single cytokine whereas Leung et al 34 tested the effect of IL-12 in the presence of IL-2, which might give potentiating effects.…”

Circulating T Cells of Patients with Active Psoriasis Respond to Streptococcal M‐Peptides Sharing Sequences with Human Epidermal Keratins

“…Superantigens have recently been shown to induce a selective expression of the skin homing receptor cutaneous-lymphocyte associated antigen, CLA [67]. Furthermore, superantigen activated mononuclear cells have been reported to induce psoriatic change in skin grafts on SCID mice [8].…”

Staphylococcal Enterotoxin B Upregulates Fas‐Mediated Apoptosis of Peripheral Blood Mononuclear Cells in Childhood Atopic Dermatitis

“…Yudate et al [19] showed that PBMCs from children with AD, demonstrated enhanced proliferation of SEB. Leung et al [20] also proposed that the Staphylococcal superantigens, secreted at the skin surface, might penetrate through the inflamed skin and stimulate Langerhans' cells to produce IL-12, upregulating the expression of CLA on T cells. Trautmann et al [21] suggested that, in peripheral blood of AD patients, both CD4 and CD8 subsets of CLA CD45RO T cells expressed upregulated Fas and FasL and underwent apoptosis.…”