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.
Leung
D Y
DY
Department of Pediatrics, National Jewish Center for Immunology and Respiratory Medicine, Denver, Colorado 80206.
Gately
M
M
Trumble
A
A
Ferguson-Darnell
B
B
Schlievert
P M
PM
Picker
L J
LJ
D000942:Antigens, Bacterial / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte; D000951:Antigens, Neoplasm; D002478:Cells, Cultured; D006801:Humans; D018664:Interleukin-12 / Q000096:biosynthesis*; D008562:Membrane Glycoproteins / Q000276:immunology*; D016201:Receptors, Lymphocyte Homing / Q000276:immunology*; D012867:Skin / Q000276:immunology*; D013211:Staphylococcus aureus / Q000276:immunology; D013291:Streptococcus / Q000276:immunology; D018089:Superantigens / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D000942:Antigens, Bacterial; D000945:Antigens, Differentiation, T-Lymphocyte; D000951:Antigens, Neoplasm; C063419:CTAGE1 protein, human; D008562:Membrane Glycoproteins; D016201:Receptors, Lymphocyte Homing; D018089:Superantigens; D018664:Interleukin-12