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*
Department of Dermatology, The Royal Free Hospital, London, United Kingdom;
Departments of Clinical Immunology and
Primary Care and Population Sciences, The Royal Free Hospital School of Medicine, London, United Kingdom; and
§
Department of Rheumatology, Birmingham University Medical School, Birmingham, United Kingdom
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-
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- 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.
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