Dominant Vγ2Vδ2 T-cell subset recognizes phosphoantigen, and exist only in humans and nonhuman primates. Despite the discovery of γδ T cells for >30 years, a proof-of-concept (POC) study has not been done to prove the principle that Vγ2Vδ2 T-cell subset is protective against M. tuberculosis (Mtb) and other infections. Here, we employed adoptive cell transfer strategy to define protective role for Vγ2Vδ2 T cells in primate TB model. Vγ2Vδ2 T cells for adoptive transfer displayed central/effector memory and mounted effector functions of producing anti-Mtb cytokines and inhibiting intracellular mycobacteria. They also expressed CXCR3/CCR5/LFA-1 trafficking/tissue-resident phenotypes and consistently trafficked to the airway and retained there detectable from 6 hours through 7 days after adoptive transfer. Interestingly, the test group of macaques receiving transfer of Vγ2Vδ2 T cells at weeks 1 and 3 after high-dose 500 CFU Mtb infection exhibited significantly lower levels of Mtb infection burdens in lung lobes and extra-pulmonary organs than the control groups receiving PBL or saline. Consistently, adoptive transfer of Vγ2Vδ2 T cells attenuated TB pathology and contained lesions mostly in the infection-site of right caudal lung lobe, with no or reduced TB dissemination to other lobes, spleens or livers/kidneys whereas the controls showed widespread TB dissemination. The POC finding supports the view that dominant Vγ2Vδ2 T-cell subset may be included for the rational design of TB vaccine or host-directed therapy.
Bone morphogenetic protein 2 (BMP2) has been shown to modulate the proliferation and differentiation of breast cancer cells. However, the biochemical effects and mechanisms remain unknown. In this paper, the effects of recombinant human BMP2 on the migration of MCF-7 cells-one breast cancer cell line, using transwell and wound healing experiments, as well as on the cellular morphology, cytoskeleton, cell surface adhesion, and stiffness detected at subcellular level by an atomic force microscope, were investigated. After BMP2 treatment, the untreated round-shaped MCF-7 cells transformed to a spindle-like shape with lots of specialized structures, such as lamellipodia, filopodia, membrane protrusions, and others, which are essential for cellular migration or spreading. Moreover, flow cytometry quantitatively detected the BMP2-induced changes in the expression of adhesion molecules, a significant rise of CD44, and a remarkable drop of E-cadherin. The data indicated that BMP2 promoted the migration and invasion of MCF-7 cells by regulating the reorganization of cytoskeleton and the expression of adhesion molecules in/on the cells. Thus, it is very imperative to evaluate the oncogenicity of BMP2 when used in tissue engineering.
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