CX(3)CR1(+) macrophages support IL-22 production by innate lymphoid cells during infection with Citrobacter rodentium.

Innate immune cells, such as intestinal epithelial cells, dendritic cells (DCs), macrophages, granulocytes, and innate lymphoid cells provide a first line of defence to enteric pathogens. To study the role of CX(3)CR1(+) DCs and macrophages in host defence, we infected CX(3)CR1-GFP animals with Citrobacter rodentium. When transgenic CX(3)CR1-GFP animals are infected with the natural mouse pathogen C. rodentium, CX(3)CR1(-/-) animals showed a delayed clearance of C. rodentium as compared with (age- and sex-matched) wild-type B6 animals. The delayed clearance of C. rodentium is associated with reduced interleukin (IL)-22 expression. In C. rodentium-infected CX(3)CR1-GFP animals, IL-22 producing lymphoid-tissue inducer cells (LTi cells) were selectively reduced in the absence of CX(3)CR1. The reduced IL-22 expression correlates with decreased expression of the antimicrobial peptides RegIIIß and RegIIIγ. The depletion of CX(3)CR1(+) cells by diphtheria toxin injection in CX(3)CR1-GFP × CD11c.DOG animals confirmed the role of CX(3)CR1(+) phagocytes in establishing IL-22 production, supporting the clearance of a C. rodentium infection.

NK- and CD8(+) T cell-mediated eradication of established tumors by peritumoral injection of CpG-containing oligodeoxynucleotides.

Unmethylated cytosine-phosphorothioate-guanine (CpG) containing oligodeoxynucleotides (CpG-ODN) are known to act as adjuvants and powerful activators of the innate immune system. We investigated the therapeutic effect of CpG-ODN on a variety of established mouse tumors including AG104A, IE7 fibrosarcoma, B16 melanoma, and 3LL lung carcinoma. These tumors are only weakly immunogenic and notoriously difficult to treat. Repeated peritumoral injection of CpG-ODN resulted in complete rejection or strong inhibition of tumor growth, whereas systemic application had only partial effects. The CpG-ODN-induced tumor rejection was found to be mediated by both NK and tumor-specific CD8(+) T cells. Comparison of parental tumors and variants rendered more antigenic by transfection with tumor Ags suggested that the efficiency of the CpG-ODN therapy correlated with the antigenicity of the tumors. Peritumoral CpG-ODN treatment was even effective in a situation where the immune system was tolerant for the tumor Ag, as shown by breakage of tolerance and tumor elimination. These results suggest that peritumoral application of CpG-ODN acts locally by inducing NK cells, and also leads to efficient presentation of tumor Ags and stimulation of CD8(+) effector and memory T cells, thus providing a powerful antitumor therapy that can be also applied without knowledge of the tumor Ag.

Impaired immune responses and altered peptide repertoire in tapasin-deficient mice.

Tapasin is a component of the major histocompatibility complex (MHC) class I antigen-loading complex. Here we show that mice with a disrupted tapasin gene display reduced MHC class I expression. Cytotoxic T cell (CTL) responses to viruses are impaired, and dendritic cells of tapasin-deficient mice do not cross-present protein antigen via the MHC class I pathway, indicating a defect in antigen processing. Natural killer (NK) cells from tapasin-deficient mice have an altered repertoire and are self-tolerant. In addition, the repertoire of class I-bound peptides is altered towards less stably binding ones. Thus tapasin plays a role in CTL and NK immune responses and in optimal peptide selection.

Principles for safety in application of neodymium-YAG laser in bronchology.

The YAG laser is being used more often in cases of nonresectable bronchogenic cancer and in some cases is called on in lieu of surgery for tracheal stenosis. Patient safety hinges first on the endoscopist's technical skill and second on his understanding of the dangers involved in laser therapy. This report is based on experience gleaned from a 1,503 case series of endoscopic YAG laser treatments on 839 patients. These treatments were carried out by seven endoscopists in four teams using exactly the same equipment and techniques. In spite of the use of this high-risk technique in a high-risk patient population comprising a majority of major airways malignancy, the mortality rate was only 0.4 percent (six deaths: all in the postoperative period). We attribute this success to careful screening prior to resection, whenever possible, and above all to our methodology which not only emphasizes prevention but also enables rapid response.

[The value of fibroscopy in laryngotracheal stenosis (author's transl)]. / Intèrêt de la fibroscopie dans les sténoses laryngo-trachéales.

The authors report the results of 297 fibroscopies in 69 patients suffering from laryngotracheal stenosis. These examinations were carried out either before treatment or for follow-up purposes. The majority of patients had undergone respiratory intensive therapy. The underlying reason for this intensive therapy was analysed, as well as the techniques used : intubation 26 %, tracheotomy 33,5 %, intubation followed by tracheotomy 40 %. Results of fibroscopy before treatment (111) are described, emphasizing the fact that this fibroscopy was adequate in the great majority of cases (96 %) to reach a decision as to wether surgery was necessary or not, and this even though certain patients had suffered severe respiratory failure. Follow-up fibroscopies (185) were useful in all cases for aspiration of the patient and observation of the suture. In 17 cases, the opportunity was taken to remove a polyp and in 10 cases removal of a suture. Finally, the authors emphasize the safety of this method of investigation (4 % of untoward incidents) which they feel to be necessary and adequate in the evaluation of laryngotracheal stenosis.,