The inhibition of cutaneous T cell apoptosis may prevent resolution of inflammation in atopic eczema.
Atopic eczema (AE) is characterized by the persistence of infiltrating T lymphocytes in the dermis. To test the hypothesis that dysregulation of normal T cell apoptosis may contribute to the pathogenesis and chronicity of AE we compared patients with a normal resolving immune response (Mantoux reaction (MR)) induced in healthy volunteers by cutaneous PPD injection. Significantly less T cell apoptosis was observed in lesional skin of AE patients compared with either the peak or the resolution phase of the MR (P < 0.0001). The low incidence of T cell apoptosis in AE was associated with significantly increased levels of Bcl-2 relative to Bax (P < 0.0001) and significantly decreased CD95-L expression (P < 0.002) compared with the resolving MR. The cytokines IL-15 and interferon-beta (IFN-beta), which prevent activated T cell apoptosis, were expressed maximally on day 7 and day 14 of the MR, respectively. In contrast, AE patients expressed high levels of both IL-15 and IFN-beta in cutaneous lesions at the same time. This suggests that the co-expression of two anti-apoptotic cytokines, which are not found together during resolving cutaneous responses, may contribute to excessive T cell survival which leads to the persistence of inflammation in patients with AE.
Orteu
C H
CH
Department of Clinical Immunology, The Royal Free and University College Medical School, London, UK.
Rustin
M H
MH
O'Toole
E
E
Sabin
C
C
Salmon
M
M
Poulter
L W
LW
Akbar
A N
AN
D000293:Adolescent; D000328:Adult; D017209:Apoptosis / Q000276:immunology; D016022:Case-Control Studies; D002455:Cell Division; D003876:Dermatitis, Atopic / Q000276:immunology / Q000473:pathology*; D005260:Female; D006801:Humans; D016899:Interferon-beta / Q000096:biosynthesis; D019409:Interleukin-15 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D012867:Skin / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology*; D014374:Tuberculin Test
D019409:Interleukin-15; D016899:Interferon-beta