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.
Orteu
C H
CH
Department of Dermatology, The Royal Free Hospital, London, United Kingdom.
Poulter
L W
LW
Rustin
M H
MH
Sabin
C A
CA
Salmon
M
M
Akbar
A N
AN
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