IL-15 knockout (KO) mice have severely reduced numbers of TCRγδ intestinal intraepithelial T lymphocytes (i-IEL), suggesting requirements of IL-15 signaling in the development or maintenance of i-IEL. To determine an involvement of survival signals via Bcl-2 in IL-15-mediated homeostasis of TCRγδ i-IEL, we introduced a bcl-2 transgene into IL-15 KO mice. In situ apoptosis of TCRγδ i-IEL was decreased in Bcl-2 transgenic (Tg) × IL-15 KO mice compared with IL-15 KO mice. The enforced expression of Bcl-2 partially restored the numbers of TCRγδ i-IEL in IL-15 KO mice. However, effector functions of TCRγδ i-IEL, including cytokine production and cytotoxic activity, were not recovered in Bcl-2 Tg × IL-15 KO mice. Importantly, TCRγδ i-IEL in Bcl-2 Tg × IL-15 KO mice expressed a reduced level of eomesodermin, a transcription factor critical for effector functions of NK cells and CD8+ T cells. Similar to the case of TCRγδ i-IEL, enforced expression of Bcl-2 restored the numbers but not the functions of NK cells in IL-15 KO mice. These results suggest that Bcl-2-mediated survival signal is involved in the IL-15-mediated homeostasis of TCRγδ i-IEL and NK cells, but other signals from IL-15 are critical for inducing transcription factors, such as eomesodermin for their effector functions.
Mice depleted of ␥␦ T cells by in vivo administration of anti-TCR␥␦ monoclonal antibodies showed susceptibility against an intravaginal infection with herpes simplex virus type 2 (HSV-2). The systemic Th1 response was impaired in the ␥␦ T-cell-depleted mice. Mice deficient in the V␦1 T subset were susceptible to an intravaginal infection with HSV-2. Intraepithelial ␥␦ T cells bearing V␦1 may help protect against intravaginal infection with HSV-2 through promoting the systemic Th1 response.
IL-15 plays a critical role in the development and maturation of gammadelta intraepithelial T lymphocytes (IEL), which are known to play important roles in wound healing and resolving inflammation in mice. In this study, we found that IL-15 transgenic (Tg) mice, under the control of a MHC Class I promoter, exhibited accelerated wound healing but were highly susceptible to genital infection with HSV-2. The IEL in the skin and reproductive organs of IL-15 Tg mice produced an aberrantly higher level of TGF-beta1 upon TCR triggering than in control mice. In vivo neutralization of TGF-beta ameliorated the susceptibility of IL-15 Tg mice to genital HSV-2 infection. Taken together, overexpression of IL-15 may stimulate IEL to produce TGF-beta1, promoting wound healing but impeding protection against genital HSV-2 infection.
Telangiectasia macularis eruptiva perstans (TMEP) is a rare form of cutaneous mastocytosis characterized by telangiectatic macules, with a generally good prognosis. 1 TMEP rarely affects young children and infants and so far has been reported as scattered or unilateral telangiectatic macules, but we report here an unusual case of linear TMEP in a five-year-old girl.A 5-year-old girl visited our hospital for pruritic eruptions that had developed on the right side of the neck, right upper arm, right hand, and left lower leg two years before ( Fig. 1a-c). There was neither a family history of the same symptom nor personal medical history.Closer examination showed linearly distributed telangiectases on the neck, right arm ( Fig. 1d), right hand, and left lower leg in a contralateral and dermatomal pattern, which seemed to be in the distribution of right C3-5, C7, T1, and left L5. The lesions were smooth to the touch on palpation. Stroking the lesion did not stimulate Darier's sign. There was no splenomegaly or lymphadenopathy.The laboratory findings, including the basophil level of the peripheral blood smear, liver transaminases, alkaline phosphatase, serous estradiol, and thyroid hormones, were within normal limits.Suspecting the possibility of acquired nevoid telangiectasia (ANT), morphea, or TMEP (linear mastocytosis), we obtained a biopsy from part of a lesion. A punch biopsy specimen from her right upper arm showed thin and markedly dilated capillaries with an abundant perivascular infiltrate of lymphocytes in the papillary dermis, without hyperpigmentation in the basal layer ( Fig. 2a). There was no remarkable sclerosis in the dermis. Both Toluidine blue stain (Fig. 2b) and Giemsa stain demonstrated scattered spindle-shaped mast cells, mainly around the dilated vessels and follicles. Based on her clinical appearance and histopathological findings, a diagnosis of TMEP was made. She was treated with beclomethasone dipropionate ointment for three months, but it failed to improve her eruptions. DiscussionTMEP is usually characterized by scattered multiple telangiectatic macules primarily involving the trunk, extremities, or face. To our knowledge, five prepubescent children with TMEP have been reported in the literature. 1-5 The first case was a 2-year-old girl with macules on the extremities and face. 1 Second and third cases were 10-year-old girls with macules on the face and extremities or the upper trunk and face. 2,3 The fourth was a 9-yearold girl with macules on the face, legs, and sacral area. 4 The fifth case was a 23-month-old boy with macules and patches on the anterior trunk and extremities. 5 To the best of our knowledge, this young girl is the first case of pediatric linear TMEP to be reported in the literature.Several adults with unilateral facial TMEP have been reported, which may mimic ANT. 6,7 ANT is usually 69 ª
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