Peptidoglycan and peptidoglycan-specific Th1 cells in psoriatic skin lesions.
We have previously demonstrated, in psoriatic skin lesions, the presence of a subset of dermal CD4+ T cells that produce interferon-gamma (IFN-gamma) in response to a mixture of cell wall proteins extracted from group A streptococci. However, the identity of the antigen(s) involved is unknown. To investigate the hypothesis that peptidoglycan (PG), the major constituent of the streptococcal cell wall, acts as a T cell activator in psoriasis, we performed in situ analysis to detect antigen-presenting cells containing PG in lesional versus non-lesional skin, and determined proliferation and IFN-gamma responses of lesional skin T cells. Increased numbers of PG-containing cells were detected in the dermal papillae and cellular infiltrates of guttate and chronic plaque skin lesions compared with normal and non-lesional psoriatic skin. A varying proportion of these were CD68+ macrophages, but the remaining cells did not double stain for either Langerhans' or dendritic cell markers. Psoriatic dermal streptococcal-specific CD4+ T cell lines proliferated and produced IFN-gamma in a self HLA-DR allele-restricted manner in response to streptococcal PG, excluding mitogenic or superantigenic stimulation, but were unresponsive to staphylococcal PG. Similarly, psoriatic staphylococcus-specific T cell lines recognized staphylococcal, but not streptococcal, PG by IFN-gamma production. The presence of PG-containing macrophages in close association with PG-specific CD4+ T cells in lesional skin suggests that PG may be responsible, at least in part, for T cell activation in psoriasis.
Department of Dermatology, Faculty of Medicine, St Mary's campus, Imperial College, London, UK.
B S
BS
Baker
J D
JD
Laman
A
A
Powles
L
L
van der Fits
J S A
JS
Voerman
M-J
MJ
Melief
L
L
Fry
D000938:Antigen-Presenting Cells / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D002460:Cell Line; D006684:HLA-DR Antigens / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007371:Interferon-gamma / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D010457:Peptidoglycan / Q000032:analysis*; D011565:Psoriasis / Q000276:immunology*; D012867:Skin / Q000166:cytology / Q000276:immunology; D013211:Staphylococcus aureus / Q000737:chemistry; D013297:Streptococcus pyogenes / Q000737:chemistry; D018417:Th1 Cells / Q000276:immunology*
D006684:HLA-DR Antigens; D010457:Peptidoglycan; D007371:Interferon-gamma