The role of apoptosis in the resolution of T cell-mediated cutaneous inflammation.
We have investigated cutaneous purified protein derivative-induced delayed-type hypersensitivity (DTH) responses in healthy volunteers to determine features associated with both the generation and resolution of the reaction. The clinical peak of the response occurred at day 3; however, T cell numbers were maximal on day 7. There was a preferential increase of CD4+ CD45RO+ T cells on day 7, which was largely due to proliferation, since a mean of 19% was in cycle. The proliferation of this subset was associated with the presence of IL-15, which was expressed as early as 12 h, and IL-2, which showed peak expression at 7 days. By day 14, there was a significant decrease in both the mean T cell number/unit area and IL-2 and IL-15 expression in perivascular infiltrates. Maximal CD95 (Fas/Apo-1) ligand and TNF-alpha expression were observed at 7 days and were associated with the presence of 1.83% (range 0.81-2.48%) apoptotic T cells. At 14 days, CD95 ligand and TNF-alpha expression were reduced significantly, and the presence of 2.5% (range 1.5-3.75%) of apoptotic T cells at this time was probably due to cytokine deprivation, associated with decreased Bcl-2 relative to Bax expression. The induction and resolution of the Mantoux reaction may depend on the expression of cytokines, such as IL-2 and IL-15, which regulate both proliferation and apoptosis in T cells. Failure to control either of these phases of the Mantoux reaction may contribute to the chronicity of inflammatory responses in certain cutaneous diseases.
Department of Dermatology, The Royal Free Hospital, London, United Kingdom.
C H
CH
Orteu
L W
LW
Poulter
M H
MH
Rustin
C A
CA
Sabin
M
M
Salmon
A N
AN
Akbar
D000328:Adult; D017209:Apoptosis / Q000276:immunology*; D015415:Biomarkers / Q000032:analysis; D002465:Cell Movement / Q000276:immunology; D016207:Cytokines / Q000032:analysis / Q000096:biosynthesis; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology / Q000473:pathology; D007249:Inflammation / Q000276:immunology; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D012867:Skin / Q000276:immunology* / Q000473:pathology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D014373:Tuberculin / Q000276:immunology; D014374:Tuberculin Test
D015415:Biomarkers; D016207:Cytokines; D014373:Tuberculin