0000000000108528
AUTHOR
Carmela La Mendola
Frequency and subset distribution of human CD8 T cells specific for mycobacterial peptides in healthy contact individuals.
A SUBSET OF VGAMMA9 VDELTA2 T CELLS HELP B CELLS FOR ANTIBODY PRODUCTION.
Differentiation, phenotype, and function of interleukin-17-producing human V{gamma}9V{delta}2 T cells
Reciprocal stimulation of gammadelta T cells and dendritic cells during the anti-mycobacterial immune response.
Gammadelta T cells and dendritic cells (DC) are two distinct cell types of innate immunity that participate in early phases of immune response against Mycobacterium tuberculosis infection. Here we show that a close functional relationship exists between these cell populations. Using an in vitro coculture system, Vgamma1 T cells from Tcrb(-/- )mice were found to be activated by DC infected in vitro with BCG, as indicated by the elevated CD69 expression, IFN-gamma secretion and cytotoxic activity. This activation process was due to a non-cognate mechanism since it required neither cell to cell contact nor interaction between the TCR and a specific antigen, but was mediated by DC-derived IL-12…
Effect of ultrasound contrast medium on human CD4+ T lymphocytes in vitro culture
CXCR5 identifies a subset of Vγ9Vδ2 T cells which secrete IL-4 and IL-10 and help B cells for antibody production
Abstract Vγ9Vδ2 T lymphocytes recognize nonpeptidic Ags and mount effector functions in cellular immune responses against microorganisms and tumors, but little is known about their role in Ab-mediated immune responses. We show here that expression of CXCR5 identifies a unique subset of Vγ9Vδ2 T cells which express the costimulatory molecules ICOS and CD40L, secrete IL-2, IL-4, and IL-10 and help B cells for Ab production. These properties portray CXCR5+Vγ9Vδ2 T cells as a distinct memory T cell subset with B cell helper function.
V gamma 9V delta 2 T lymphocytes efficiently recognize and kill zoledronate-sensitized, imatinib-sensitive, and imatinib-resistant chronic myelogenous leukemia cells.
Abstract Imatinib mesylate (imatinib), a competitive inhibitor of the BCR-ABL tyrosine kinase, is highly effective against chronic myelogenous leukemia (CML) cells. However, because 20–30% of patients affected by CML display either primary or secondary resistance to imatinib, intentional activation of Vγ9Vδ2 T cells by phosphoantigens or by agents that cause their accumulation within cells, such as zoledronate, may represent a promising strategy for the design of a novel and highly innovative immunotherapy capable to overcome imatinib resistance. In this study, we show that Vγ9Vδ2 T lymphocytes recognize, trogocytose, and efficiently kill imatinib-sensitive and -resistant CML cell lines pre…
Memory and effector CD8 T cell subsets in human tuberculosis.
Efficient Killing of Human Colon Cancer Stem Cells by γδ T Lymphocytes
Abstract Colon cancer comprises a small population of cancer stem cells (CSC) that is responsible for tumor maintenance and resistant to cancer therapies, possibly allowing for tumor recapitulation once treatment stops. We previously demonstrated that such chemoresistance is mediated by autocrine production of IL-4 through the up-regulation of antiapoptotic proteins. Several innate and adaptive immune effector cells allow for the recognition and destruction of cancer precursors before they constitute the tumor mass. However, cellular immune-based therapies have not been experimented yet in the population of CSCs. Here, we show that the bisphosphonate zoledronate sensitizes colon CSCs to Vγ9…
Human CD4 T-Cells With a Naive Phenotype Produce Multiple Cytokines During Mycobacterium Tuberculosis Infection and Correlate With Active Disease
T-cell-mediated immune responses play a fundamental role in controlling Mycobacterium tuberculosis (M. tuberculosis) infection, and traditionally, this response is thought to be mediated by Th1-type CD4+ T-cells secreting IFN-γ. While studying the function and specificity of M. tuberculosis-reactive CD4+ T-cells in more detail at the single cell level; however, we found a human CD4+ T-cell population with a naive phenotype that interestingly was capable of producing multiple cytokines (TCNP cells). CD4+ TCNP cells phenotyped as CD95lo CD28int CD49dhi CXCR3hi and showed a broad distribution of T cell receptor Vβ segments. They rapidly secreted multiple cytokines in response to different M. t…
Changes in the morphology of sea urchin embryos exposed during specific stages of development to 50 Hz electric and magnetic fields
EFFECTS OF THE STATIC MAGNETIC FIELD GENERATED BY 0.5 T MRI UNIT ON TNF-alpha RELEASE OF HUMAN PBMC FROM PATIENTS WITH RHEUMATOID ARTHRITIS.
Cross-talk between human myeloid dendritic cells and VG9VD2 T cells during M. tuberculosis infection.
Aminobisphosphonate-activated γδ T cells in immunotherapy of cancer: doubts no more
BACKGROUND: Activated V gamma 9 V delta 2 T cells are able to kill most tumour cells because of recognition by T cell receptor and natural killer receptors. OBJECTIVE: We discuss the possibility that the intentional activation of gammadelta T cells in vivo by aminobisphosphonates may represent a promising target for the design of novel and highly innovative immunotherapy in cancer patients. METHODS: The antitumoral effects of gammadelta T cells both in vitro and in vivo have been demonstrated suggesting a new therapeutic approach for translation into the clinical setting. RESULTS/CONCLUSION: V gamma 9 V delta 2 T lymphocytes represent a particularly interesting target for immunotherapeutic …
Reversible effect of MR and ELF magnetic fields (0.5 T and 0.5 mT) on human lymphocyte activation patterns.
Purpose: The aim of this study was to investigate the effects of magnetic fields (MF) of different intensity generated by a magnetic resonance (MR) unit (0.5 Tesla) and a double cylindrical coil (0.5 mTesla) on human CD4+ T cell lines. Materials and methods: CD4+ T cells were exposed for two hours under isothermal conditions (37 ± 0.5°C) to the above mentioned MF; a control group was provided for each exposed sample. After exposure, the samples were analysed in the laboratory for the following endpoints: Release of cytokines, expression of surface markers, cell proliferation and levels of cytosolic free-calcium. Results: Exposure to MF for 2 h and subsequent in vitro stimulation in the pres…
Differentiation, phenotype, and function of interleukin-17-producing human Vγ9Vδ2 T cells.
Abstract In healthy adults, the major peripheral blood γδ T-cell subset expresses the Vγ9Vδ2 TCR and displays pleiotropic features. Here we report that coculture of naive Vγ9Vδ2 T cells with phosphoantigens and a cocktail of cytokines (IL-1-β, TGF-β, IL-6, and IL-23), leads to selective expression of the transcription factor RORγt and polarization toward IL-17 production. IL-17+ Vγ9Vδ2 T cells express the chemokine receptor CCR6 and produce IL-17 but neither IL-22 nor IFN-γ; they have a predominant terminally differentiated (CD27−CD45RA+) phenotype and express granzyme B, TRAIL, FasL, and CD161. On antigen activation, IL-17+ Vγ9Vδ2 T cells rapidly induce CXCL8-mediated migration and phagocy…
Vγ9Vδ2 T cells as a promising innovative tool for immunotherapy of hematologic malignancies
The potent anti-tumor activities of γδ T cells, their ability to produce pro-inflammatory cytokines, and their strong cytolytic activity have prompted the development of protocols in which γδ agonists or ex vivo-expanded γδ cells are administered to tumor patients. γδ T cells can be selectively activated by either synthetic phosphoantigens or by drugs that enhance their accumulation into stressed cells as aminobisphosphonates, thus offering new avenues for the development of γδ T cell-based immunotherapies. The recent development of small drugs selectively activating Vγ9Vδ2 T lymphocytes, which upregulate the endogenous phosphoantigens, has enabled the investigators to design the experiment…
EFFECTS OF ELECTROMAGNETIC FIELDS ON IFN-GAMMA RELEASE AND CONTENENT FROM HUMAN SUBSETS OF CD4+T CELLS.
Differentiation of human Vgamma9 Vdelta 2 T cell subsets by antigen or homeostatic cytokines
THE ROLE OF GAMMA-DELTA (γδ) T LYMPHOCYTES IN MELANOMA: BASIC SCIENCE FINDINGS AND CLINICAL CORRELATIONS
INTRODUCTION: Advanced melanoma is associated with a poor prognosis. Numerous clinical trials have focused on the potential of tumor-infiltrating lymphocytes (TILs) for immunotherapy in stage III and IV melanoma, but its treatment remains challenging. Gamma-delta (γδ) T cells are the most represented subpopulation of TILs and have shown therapeutic potentials in many solid tumors, although their role against melanoma has not been fully investigated. MATERIALS AND METHODS: Seventy-four patients with cutaneous melanoma underwent peritumoral skin biopsies and blood sample collection. TILs and circulating lymphocytes phenotype and effector functions were analzyed using immunohistochemistry and …
Differentiation of human CD8+ T cells in BCG vaccinated and tuberculous patients.
Characterization of HLA-DR- and TCR-binding residues of an immunodominant and genetically permissive peptide of the 16-kDa protein of Mycobacterium tuberculosis.
The 16-kDa protein of Mycobacterium tuberculosis represents an important antigenic target during bacillary latency and, consequently, should be considered as candidate subunit vaccine component. In this study, we have used CD4 T cell clones that recognize the peptide p91-110, an immunodominant and genetically permissive epitope, in the context of five different HLA-DR molecules and truncated and substituted variants of this peptide, to identify the minimal binding sequence (HLA-DR-binding core) and the minimal stimulatory sequence (TCR-binding core), as well as the residues that contact HLA-DR molecules and the TCR. We have found a common 9-mer sequence, spanning amino acids 93-101, as the …
Characterization of Human γδ T Lymphocytes Infiltrating Primary Malignant Melanomas
T lymphocytes are often induced naturally in melanoma patients and infiltrate tumors. Given that gamma delta T cells mediate antigen-specific killing of tumor cells, we studied the representation and the in vitro cytokine production and cytotoxic activity of tumor infiltrating gamma delta T cells from 74 patients with primary melanoma. We found that gamma delta T cells represent the major lymphocyte population infiltrating melanoma, and both V delta 1(+) and V delta 2(+) cells are involved. The majority of melanoma-infiltrating gamma delta cells showed effector memory and terminally-differentiated phenotypes and, accordingly, polyclonal gamma delta T cell lines obtained from tumor-infiltrat…
The expanding universe of gamma delta T lymphocytes: subsets, generation and function
Characterization of HLA-DR- and TCR-binding residues of an immunodominant and genetically permissive peptide of the 16-kDa protein of Mycobacterium tuberculosis
EFFECTS OF THE STATIC MAGNETIC FIELD GENERATED BY A 1.5 T MRI UNIT ON TNF ALFA RELEASE AND TNF RECEPTOR II EXPRESSION OF HUMAN MONOCYTES.
Effects of the static magnetic field generated by a 1,5 T MRI unit on TNF-a release and TNF-receptor II expression of human monocyes
Memory and effector CD8 T cell subset in human tuberculosis.
Reversible effect of magnetic fields on human lymphocyte activation patterns: different sensitivity of naive and memory lymphocyte subsets.
The aim of this study was to investigate the influence of 50 Hz magnetic or static magnetic fields of 0.5 mT on subsets of human CD4(+) T cells in terms of cytokine release/content, cell proliferation and intracellular free calcium concentration. CD4(+) T cells can be divided into different subsets on the basis of surface marker expression, such as CD45, and T cells can be divided into naive (CD45RA(+)) and memory (CD45RA(-)) cells. In this study, the effects of magnetic fields after 24 and 48 h of cell culture were analyzed. We found that the CD4(+)CD45RA(-) T subset were more sensitive after 2 h of exposure. Decreases in the release/content of IFN-gamma, in cell proliferation and in intra…
CXCR5 identifies a subset of Vgamma9 Vdelta2 T cells which secrete IL-4 and IL-10 and help B cells for antibody production.
Vgamma9Vdelta2 T lymphocytes recognize nonpeptidic Ags and mount effector functions in cellular immune responses against microorganisms and tumors, but little is known about their role in Ab-mediated immune responses. We show here that expression of CXCR5 identifies a unique subset of Vgamma9Vdelta2 T cells which express the costimulatory molecules ICOS and CD40L, secrete IL-2, IL-4, and IL-10 and help B cells for Ab production. These properties portray CXCR5+ Vgamma9Vdelta2 T cells as a distinct memory T cell subset with B cell helper function.
Phenotypical and functional analysis of memory and effector human CD8 T cells specific for mycobacterial antigens
Abstract Mycobacterium tuberculosis infects one-third of the global population and claims two million lives every year. Because memory CD8 T cells exhibit a high heterogeneity in terms of phenotype and functional characteristic, we investigated the frequency, phenotype, and functional properties of Ag85A epitope-specific HLA-A*0201 CD8 T cells in children affected by tuberculosis (TB) before and 4 mo after chemotherapy and healthy contact children. Using Ag85A peptide/HLA-A*0201 pentamer, we found a low frequency of blood peptide-specific CD8 T cells in tuberculous children before therapy, which consistently increased after therapy to levels detected in healthy contacts. Ex vivo analysis of…