The utility of ultrasound superb microvascular imaging for evaluation of breast tumour vascularity: comparison with colour and power Doppler imaging regarding diagnostic performance.

AIM: To investigate the utility of superb microvascular imaging (SMI) for evaluating the vascularity of breast masses in comparison with colour or power Doppler ultrasound (US) and the effect on diagnostic performance. MATERIALS AND METHODS: A total of 191 biopsy-proven masses (99 benign and 92 malignant) in 166 women with greyscale, colour Doppler, power Doppler, and SMI images were enrolled in this retrospective study. Three radiologists analysed the vascular images using a three-factor scoring system to evaluate the number, morphology, and distribution of tumour vessels. They assessed the Breast Imaging-Reporting and Data System categories for greyscale US alone and combinations of greyscale US and each type of vascular US. The Kruskal-Wallis test was performed and the area under the receiver-operating characteristic curve (AUC) measured. On SMI, vascular scores were compared between benign and malignant masses and the optimal cut-off value for the overall score was determined. RESULTS: SMI showed higher vascular scores than colour or power Doppler US and malignant masses had higher scores than benign masses (p<0.001). The diagnostic performance of the combination of greyscale US and SMI was higher than those of greyscale US alone and greyscale and colour or power Doppler US (AUC, 0.815 versus 0.774, 0.789, 0.791; p<0.001). The optimal cut-off value of the overall vascular score was 5 with a sensitivity of 82.3% and a specificity of 65.3% (AUC, 0.808). CONCLUSION: SMI is superior to colour or power Doppler US for characterising the vascularity in breast masses and improving diagnostic performance.

Il-12: keeping cell-mediated immunity alive.

Interleukin (IL)-12 has dominated the field of cell-mediated immunity since its discovery more than 10 years ago, and clearly plays an essential role in the development of Th1 cells under a variety of conditions. Recent studies now indicate that the importance of IL-12 is not limited to initiating an immune response, but may contribute to maintaining immunity. Thus, Th1 responses rapidly wane in the absence of IL-12, leading to a loss in protective immunity against intracellular pathogens, such as Leishmania and Toxoplasma. Determining how IL-12 maintains Th1 cells, and consequently cell-mediated immunity, will provide new insights useful in controlling the immune response, and may thus influence the design of new vaccines and immunotherapies.

Maintenance of IL-12-responsive CD4+ T cells during a Th2 response in Leishmania major-infected mice.

BALB/c and anti-IL-12-treated C3H mice infected with Leishmania major develop a Th2 cell response. However, in contrast to BALB/c mice, C3H mice treated transiently with an anti-IL-12 monoclonal antibody switch from a Th2 to a Th1 response and resolve their lesions once treatment is terminated. We report here that the critical difference in the Th2 response between BALB/c and C3H mice is in their ability to respond to IL-12. Thus, C3H mice with a Th2 response maintain a CD4+ T cell population that expresses IL-12 receptor beta1 and beta2 mRNA and produces IFN-gamma after exposure to IL-12. These results indicate that Th2 cell populations from different genetic backgrounds differ in their stability, and that this difference can be related to differential regulation of the IL-12 receptor.

IL-12 is required to maintain a Th1 response during Leishmania major infection.

IL-12 initiates Th1 cell development and cell-mediated immunity, but whether IL-12 contributes to the maintenance of a Th1 response is unclear. To address this question, we infected IL-12 p40-/- C57BL/6 mice with Leishmania major, an intracellular protozoan parasite controlled by a cell-mediated immune response, and simultaneously administered IL-12. Whereas untreated p40-/- mice developed an uncontrolled infection, p40-/- mice treated with IL-12 for the first 2 or 4 wk of infection developed a Th1 response and resolved their lesions. However, the induction of this protective Th1 cell response by IL-12 treatment was not associated with long term immunity. We observed that on rechallenge in the absence of IL-12, the mice exhibited a susceptible phenotype. In addition, without rechallenge, lesions in the IL-12-treated p40-/- mice developed several weeks after cessation of IL-12 treatment. In both cases, disease was associated with the loss of a Th1 response and the development of a Th2 response. Our observations are not limited to the C57BL/6 strain, because IL-12 treatment was also unable to provide lasting protection to p40-/- BALB/c mice. Finally, we found that although Th1 cells from healed wild-type C57BL/6 mice adoptively transferred protection to L. major-infected RAG-/- mice, they were unable to protect p40-/- mice. In conclusion, these studies provide the first demonstration that IL-12 is required not only to initiate Th1 cell development but also throughout infection to maintain a Th1 cell response and resistance to L. major.

Lymphoid hyperplasia, autoimmunity, and compromised intestinal intraepithelial lymphocyte development in colitis-free gnotobiotic IL-2-deficient mice.

IL-2-deficient (IL-2(-/-)) mice develop disorders of the hemopoietic and immune systems characterized by anemia, lymphocytic hyperplasia, and colitis. The mechanisms responsible for these abnormalities remain unclear. To investigate the underlying basis of autoimmunity, the particular role of commensal gut flora in the initiation of colitis, and the role of IL-2 in the development of intestinal intraepithelial lymphocytes (iIEL), we evaluated IL-2(-/-) mice reared and maintained under gnotobiotic (germfree) conditions. By 8 wk of age, 80% (20 of 25) of germfree IL-2(-/-) mice show signs of disease, including anemia, disturbances in bone marrow hemopoietic cells, lymphocytic hyperplasia, and generalized autoimmunity, similar to those seen in specific pathogen-free (SPF) IL-2(-/-) mice. In striking contrast to SPF IL-2(-/-) mice, germfree IL-2(-/-) mice do not develop colitis. However, the numbers of gammadelta+ and TCR alphabeta+ CD8 alphaalpha+ iIELs are reduced, and in lethally irradiated SPF IL-2(+/+) mice, reconstituted with IL-2(-/-) bone marrow TCR gammadelta+ iIELs fail to develop, consistent with an important role of IL-2/IL-2R signaling in the development of gammadelta iIELs. Consequently, our findings demonstrate that the colitis seen in SPF IL-2(-/-) mice depends upon the presence of intestinal bacterial flora and that environmental Ags are not responsible for the anemia and extraintestinal lymphoid hyperplasia that occur in IL-2(-/-) mice. Thus, germfree IL-2(-/-) mice represent a unique system in which the role of IL-2 deficiency in hemopoietic and immune system disorders can be investigated in dissociation from complications that may arise due to colitis.