The superantigen exfoliative toxin induces cutaneous lymphocyte-associated antigen expression in peripheral human T lymphocytes.

Several immune-mediated dermatoses including psoriasis and atopic dermatitis can be exacerbated by bacterial infections. Superantigen producing bacteria can be isolated from skin lesions of these dermatoses. Consistent with superantigen effects, skewed T cell receptor variable gene usage has been demonstrated within these lesions. Therefore, the question arises whether superantigen induce a skin-seeking phenotype within peripheral T cells. In this study, we investigated the in vitro influence of the V beta 2-selective superantigen exfoliative toxin from Staphylococcus aureus on the expression of the cutaneous lymphocyte-associated antigen on peripheral T lymphocytes of healthy donors. We demonstrate that exfoliative toxin dramatically upregulates cutaneous lymphocyte-associated antigen expression on T cell receptor V beta 2+ lymphocytes. Up to 69% of V beta 2+ lymphocytes expressed cutaneous lymphocyte-associated antigen after 5 days of in vitro culture. Additionally, exfoliative toxin also increased cutaneous lymphocyte-associated antigen expression in CD3+ T cell receptor V beta 2- lymphocytes indicating a different effect as caused by the superantigen-T cell receptor V beta 2 interaction. Our findings suggest influence of bacterial superantigens on T lymphocyte skin homing in vivo.

Superantigens but not mitogens are capable of inducing upregulation of E-selectin ligands on human T lymphocytes.

Bacterial infections can exacerbate immune mediated dermatoses, possibly via superantigens produced by these bacteria. Therefore, we asked whether superantigens induce the expression of adhesion molecules which may then facilitate invasion of highly activated T cells into different organs. The influence of exfoliative toxin (ET) and toxic shock syndrome toxin-1 (TSST-1) stimulation on the expression of a broad panel of adhesion and costimulatory molecules was investigated by flow cytometry. We found that only the E-selectin ligands cutaneous lymphocyte-associated antigen (CLA) and sialylated Lewis(x) (CD15s) are significantly upregulated by these superantigens but not by mitogen stimulation. In contrast, the mucosal lymphocyte-associated antigen (MLA) recognized by the monoclonal antibody Ber-Act8 was not differentially induced by mitogen or superantigen stimulation. Therefore, T lymphocyte stimulation by bacterial superantigens might directly influence their skin homing capacity. Furthermore, the superantigen-driven induction of CD15s-an adhesion molecule which is absent or only weakly expressed by resting or mitogen stimulated T cells-may indicate a role of this antigen for T cell skin homing. An additional adhesion pathway via E-selectin may thus be available to lymphocytes, comparable to granulocytes which constitutively express CD15s.