The chemokine receptor CXCR3 has been shown to play a key role in the recruitment of T cells to sites of inflammation such as allografts. Here, we investigated which signals and conditions areresponsible for CXCR3 induction. CXCR3 was induced on T cells that were stimulated with anti‐CD3 plus anti‐CD28 monoclonal antibodies and then recultured without any external stimuli. CXCR3 expression was inhibited when TCR stimulation was persistent in the reculture. CXCR3 induction also depended on the stimulation with IFN‐γ because CXCR3 expression was not induced in IFN‐γ‐deficient T cells. The induction of another Th1 chemokine receptor CCR5 absolutely required IL‐12 stimulation and STAT4 involvement. In contrast, CXCR3 was induced on STAT4‐deficient T cells independently of IL‐12 stimulation as long as IFN‐γ was produced as a result of potent TCR stimulation. These results show that CXCR3 induction on TCR‐triggered T cells requires the release of these T cells from persistent TCR signaling and the stimulation with IFN‐γ and also indicate the differential regulatory mechanisms underlying the induction of two Th1 chemokine receptors.

T helper cell type 1 (Th1) and Th2 cells express distinct sets of chemokine receptors. In contrast to Th1 chemokine receptors, it is largely unknown how Th2 chemokine receptors such as CC chemokine receptor 4 (CCR4) are induced during Th2 differentiation. Here, we investigated the induction of CCR4 surface expression and ligand responsiveness evaluated by functional assays such as chemokine binding and chemotaxis. This was done in comparison with those of a Th1 chemokine receptor, CXC chemokine receptor 3 (CXCR3). Resting T cells expressed neither CXCR3 nor CCR4. CXCR3 expression and ligand responsiveness were observed when resting T cells were stimulated with anti-CD3 plus anti-CD28 in the presence of [interleukin (IL)-12+anti-IL-4] and then recultured without T cell receptor (TCR) stimulation. Unlike CXCR3, CCR4 was induced immediately after anti-CD3/anti-CD28 stimulation in the presence of (IL-4+anti-interferon-gamma+anti-IL-12). However, these CCR4-positive cells failed to exhibit chemokine binding and chemotaxis. Although the levels of surface CCR4 expression were not increased after the subsequent reculture in the absence of TCR stimulation, CCR4 responsiveness was induced in this stage of Th2 cells. The induction of CCR4 expression and the acquisition of CCR4 responsiveness did not occur in IL-4-deficient (IL-4(-/-)) and signal transducer and activator of transcription (STAT)6(-/-) T cells. CCR4 expression and functionality were regained in IL-4(-/-) but not in STAT6(-/-) T cells by the addition of recombinant IL-4. Although surface expression and functionality of CCR4 are induced depending on the IL-4/STAT6 signaling pathway, the present results indicate that the functionality of CCR4 does not correlate with CCR4 expression but emerges at later stages of Th2 differentiation.

We report a case of maxillary gingival metastasis from lung cancer, the first symptom of which occurred in an oral cavity. The patient was an 80-year-old man. On his initial visit, a soft elastic mass, with an 18mm diameter, was on his right maxillary gingiva. A biopsy revealed the lesion was a large cell carcinoma. Since the large cell carcinoma is less likely to firstly occur in the gingiva, we inspected the whole body of the patient. As a result, tumors were found in the upper left lung, stomach and brain. The metastatic gingival tumor increased rapidly after the biopsy. We conducted concurrent chemoradiotherapy using S-1 with a total dose of 38.4Gy irradiation to the oral and brain lesion. This treatment reduced the maxillary gingival tumor. He died from a stroke ; however, due to reduction of the gingival tumor, he could continue to have oral nutrition until immediately before his death. It was suggested that we should consider palliative chemoradiotherapy for a maxillary gingival metastasis, even if it was impossible to cure the patient to maintain his Quality of Life.

No abstract

No abstract