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cd4 ctl

Denis R Chopera, Roman Ntale, Nonkululeko Ndabambi, Nigel Garrett, Clive M Gray, David Matten, Quarraisha Abdool Karim, Salim Abdool Karim, Carolyn Williamson
OBJECTIVE: HIV-1 escape from cytotoxic T-lymphocytes (CTL) results in the accumulation of HLA-associated mutations in the viral genome. To understand the contribution of early escape to disease progression, this study investigated the evolution and pathogenic implications of CTL escape in a cohort followed from infection for five years. METHODS: Viral loads and CD4+ counts were monitored in 78 subtype C infected individuals from onset of infection until CD4+ decline to <350 cells/μl or five years post-infection...
October 14, 2016: AIDS
Jing Li, Lanzhu Yue, Huaquan Wang, Chunyan Liu, Hui Liu, Jinglian Tao, Weiwei Qi, Yihao Wang, Wei Zhang, Rong Fu, Zonghong Shao
Th17 cells are a newly found subset of distinct CD4+ Th effector cells' family and are found to play an important role in cancers. Myelodysplastic syndromes (MDS) are a common malignant hematological disease. Here, we showed that both the percentage and the function of Th17 cells were elevated in low-risk MDS while being decreased in high-risk MDS. Levels of upstream molecules of Th17 cells, IL-6 and IL-23, were higher in low-risk MDS but lower in high-risk MDS patients. The abnormal percentage of Th17 cells was closely related to clinical parameters including karyotype, morphologic blast percentage of bone marrow, peripheral absolute neutrophil count, and hemoglobin concentration...
2016: Journal of Immunology Research
Mohammad Heidari, Dan Wang, Phillip Delekta, Shuhong Sun
Marek's disease virus (MDV), a highly cell-associated lymphotropic α-herpesvirus, is the causative agent of Marek's disease (MD) in domestic chickens. MDV replicates in chicken lymphocytes and establishes a latent infection within CD4(+) T cells. The latently infected CD4(+) T cells carry the virus to visceral organs, peripheral nerves, and feather follicle epithelium (FFE). FFE is the only anatomical site where infectious enveloped cell-free virus particles are produced and disseminated into the environment...
November 1, 2016: Veterinary Immunology and Immunopathology
Huanyu Ju, Wenjing Xing, Jinfeng Yang, Yang Zheng, Xiuzhi Jia, Benning Zhang, Huan Ren
BACKGROUND: Despite recent advances in early detection and improvements in chemotherapy for colon cancer, the patients still face poor prognosis of postoperative recurrence and metastasis, the median survival for patients with metastatic colorectal cancer is approximately 22-24 months. Some immunotherapeutic approaches had been attempted in colon cancer patients to significantly increase overall survival. A vaccine based approach has shown a novel direction for colon cancer prevention and therapy...
September 26, 2016: BMC Immunology
C Mee Ling Munier, David van Bockel, Michelle Bailey, Susanna Ip, Yin Xu, Sheilajen Alcantara, Sue Min Liu, Gareth Denyer, Warren Kaplan, Kazuo Suzuki, Nathan Croft, Anthony Purcell, David Tscharke, David A Cooper, Stephen J Kent, John J Zaunders, Anthony D Kelleher
BACKGROUND: Smallpox was eradicated by a global program of inoculation with Vaccinia virus (VV). Robust VV-specific CD4 T-cell responses during primary infection are likely essential to controlling VV replication. Although there is increasing interest in cytolytic CD4 T-cells across many viral infections, the importance of these cells during acute VV infection is unclear. METHODS: We undertook a detailed functional and genetic characterization of CD4 T-cells during acute VV-infection of humans...
October 17, 2016: Vaccine
Marilia Rita Pinzone, Erin Graf, Lindsay Lynch, Brigit McLaughlin, Frederick M Hecht, Mark Connors, Stephen A Migueles, Wei-Ting Hwang, Giuseppe Nunnari, Una O'Doherty
: The dynamics of HIV reservoir accumulation off antiretroviral therapy (ART) is underexplored. Levels of integrated HIV DNA in peripheral blood mononuclear cells (PBMCs) were longitudinally monitored before and after antiviral therapy. HIV integration increased over time in both Elite Controllers (ECs, n=8) and Non-Controllers (NCs, n=6) before ART, whereas integration remained stable in patients on ART (n=4). The median annual fold-change was higher in NCs compared to ECs and negatively correlated with CD4/CD8 T-cell ratio...
September 14, 2016: Journal of Virology
Masahiro Azuma, Yohei Takeda, Hiroko Nakajima, Haruo Sugiyama, Takashi Ebihara, Hiroyuki Oshiumi, Misako Matsumoto, Tsukasa Seya
Successful cancer immunotherapy necessitates T cell proliferation and infiltration into tumor without exhaustion, a process closely links optimal maturation of dendritic cells (DC), and adjuvant promotes this process as an essential prerequisite. Poly(I:C) has contributed to adjuvant immunotherapy that evokes an antitumor response through the Toll-loke receptor 3 (TLR3)/TICAM-1 pathway in DC. However, the mechanism whereby Poly(I:C) acts on DC for T cell proliferation and migration remains undetermined. Subcutaneous injection of Poly(I:C) regressed implant tumors (WT1-C1498 or OVA-EG7) in C57BL/6 mice, which coincided with tumor-infiltration of CD8(+) T cells...
August 2016: Oncoimmunology
Kunyu Li, Margaret Baird, Jianping Yang, Chris Jackson, Franca Ronchese, Sarah Young
Adoptive cell therapies (ACTs) using tumor-reactive T cells have shown clinical benefit and potential for cancer treatment. While the majority of the current ACT are focused on using CD8(+) cytotoxic T lymphocytes (CTL), others have shown that the presence of tumor-reactive CD4(+) T helper (Th) cells can greatly enhance the anti-tumor activity of CD8(+) CTL. However, difficulties in obtaining adequate numbers of CD4(+) Th cells through in vitro expansion can limit the application of CD4 Th cells in ACT. This study aims to optimize the culture conditions for mouse CD4 T cells to provide basic information for animal studies of ACT using CD4 T cells...
August 2016: Clinical & Translational Immunology
Manli Wu, Min Li, Yan Yue, Wei Xu
DNA-based vaccine is a promising candidate for immunization and induction of a T-cell-focused protective immune response against infectious pathogens such as Mycobacterium tuberculosis (M. tb). To induce multi-functional T response against multi-TB antigens, a multi-epitope DNA vaccine and a 'protein backbone grafting' design method is adopted to graft five discontinuous T-cell epitopes into HSP65 scaffold protein of M. tb for enhancement of epitope processing and immune presentation. A DNA plasmid with five T-cell epitopes derived from ESAT-6, Ag85B, MTB10...
September 2016: Microbiology and Immunology
Matthew Pace, James Williams, Ayako Kurioka, Andrew B Gerry, Bent Jakobsen, Paul Klenerman, Nneka Nwokolo, Julie Fox, Sarah Fidler, John Frater
In the search for a cure for HIV-1 infection, histone deacetylase inhibitors (HDACi) are being investigated as activators of latently infected CD4 T cells to promote their targeting by cytotoxic T-lymphocytes (CTL). However, HDACi may also inhibit CTL function, suggesting different immunotherapy approaches may need to be explored. Here, we study the impact of different HDACi on both Natural Killer (NK) and CTL targeting of HIV-1 infected cells. We found HDACi down-regulated HLA class I expression independently of HIV-1 Nef which, without significantly compromising CTL function, led to enhanced targeting by NK cells...
August 2016: PLoS Pathogens
W Herr, Y Eichinger, J Beshay, A Bloetz, S Vatter, C Mirbeth, E Distler, U F Hartwig, S Thomas
Refractory or relapsed acute myeloid leukemia (AML) represents a frequent complication after allogeneic hematopoietic stem-cell transplantation (HSCT). We show herein that primary in vitro stimulation of CD45RA-selected CD4 T cells of stem-cell donors with 10/10 HLA-matched AML blasts results in expansion of cytolytic T-lymphocytes (CTL) that almost all recognize HLA-DPB1 mismatch alleles, which clinically occur in up to 80% of donor-patient pairs. Primary AML blasts were found to strongly express HLA-DPB1, whereas fibroblasts and keratinocytes used as surrogate target cells for graft-versus-host disease did express HLA-DPB1 only upon IFN-γ pre-treatment...
September 2, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Sylvain Ladoire, Laura Senovilla, David Enot, François Ghiringhelli, Vichnou Poirier-Colame, Kariman Chaba, Gulsun Erdag, Jochen T Schaefer, Donna H Deacon, Laurence Zitvogel, Craig L Slingluff, Guido Kroemer
Melanoma is known to be under latent immunosurveillance. Here, we studied four biomarkers of immunogenic cell stress and death (microtubule-associated proteins 1A/1B light chain 3B (MAP-LC3B, best known as LC3B)-positive puncta in the cytoplasm as a sign of autophagy; presence of nuclear HMGB1; phosphorylation of eIF2α; increase in ploidy) in melanoma cells, in tissue microarrays (TMA) from metastases from 147 melanoma patients. These biomarkers of immunogenicity were correlated with the density of immune cells infiltrating the metastases and expressing CD3, CD4(+), CD8(+), CD20, CD45, CD56, CD138, CD163, DC-LAMP or FOXP3...
June 2016: Oncoimmunology
Neda Mousavi Niri, Arash Memarnejadian, Younes Pilehvar-Soltanahmadi, Mohammadreza Agha Sadeghi, Mehdi Mahdavi, Nasim Kheshtchin, Samaneh Arab, Afshin Namdar, Farhad Jadidi, Nosratollah Zarghami, Jamshid Hajati
INTRODUCTION: The critical role of regulatory T (Treg) cells in dampening immune responses against tumor cells is apparent. Therefore, several methods have been introduced for eliminating Treg. Among them, inducing immune responses against Treg cells expressing Foxp3 transcription factor is a hopeful approach to decrease the frequency of Tregs. In current study, we used the chimeric FoxP3-Fc(IgG) fusion construct/protein to effectively stimulate the immune responses against Treg cells...
September 2016: Journal of Immunotherapy
Arvind Chhabra, Bijay Mukherji
Regulatory T cells (Treg) can interfere with the generation and function of anti-tumor immune effectors. Accordingly, ways that could block Treg function would be useful in cancer immunotherapy. We have previously shown that incorporation of CD4+CD25-ve T cells in an in vitro cytolytic T lymphocyte (CTL) generation assay leads to generation of induced regulatory T cells (iTregs), and that these iTreg block the generation of productive CTL response (Chattopadhyay et al., 2006). We here show that human CD4 T cells engineered to express MHC class I-restricted human melanoma associated epitope, MART-127-35, specific T cell receptor (TCR), that can simultaneously exhibit helper as well as cytolytic effector functions (Chhabra et al...
October 2016: Human Immunology
Sammy Bedoui, William R Heath, Scott N Mueller
CD8(+) T cells provide an important component of protection against intracellular infections and cancer. Immune responses by these T cells involve a primary phase of effector expansion and differentiation, followed by a contraction phase leading to memory formation and, if antigen is re-encountered, a secondary expansion phase with more rapid differentiation. Both primary and secondary phases of CD8(+) T-cell immunity have been shown to depend on CD4(+) T-cell help, although during certain infections the primary phase is variable in this requirement...
July 2016: Immunological Reviews
Rong Wang, Aizhang Xu, Xueying Zhang, Jie Wu, Andrew Freywald, Jianqing Xu, Jim Xiang
CD8(+) cytotoxic T lymphocyte (CTL) exhaustion is a chief issue for ineffective virus elimination in chronic infectious diseases. We generated novel ovalbumin (OVA)-specific OVA-Texo and HIV-specific Gag-Texo vaccines inducing therapeutic immunity. To assess their therapeutic effect in chronic infection, we developed a new chronic infection model by i.v. infecting C57BL/6 mice with the OVA-expressing adenovirus AdVova. During chronic AdVova infection, mouse CTLs were found to express the inhibitory molecules programmed cell-death protein-1 (PD-1) and lymphocyte-activation gene-3 (LAG-3) and to be functionally exhausted, showing a significant deficiency in T-cell proliferation, IFN-γ production and cytolytic effects...
June 6, 2016: Cellular & Molecular Immunology
Kellie N Smith, Robbie B Mailliard, Paolo A Piazza, Will Fischer, Bette T Korber, Ronald J Fecek, Deena Ratner, Phalguni Gupta, James I Mullins, Charles R Rinaldo
UNLABELLED: Curing HIV-1 infection will require elimination of persistent cellular reservoirs that harbor latent virus in the face of combination antiretroviral therapy (cART). Proposed immunotherapeutic strategies to cure HIV-1 infection include enhancing lysis of these infected cells by cytotoxic T lymphocytes (CTL). A major challenge in this strategy is overcoming viral immune escape variants that have evaded host immune control. Here we report that naive CD8(+) T cells from chronic HIV-1-infected participants on long-term cART can be primed by dendritic cells (DC)...
2016: MBio
Masatoshi Hirayama, Yasuharu Nishimura
Tumor cells commonly express several antigens, such as tumor-associated antigens (TAAs) or mutation-derived antigens (neoantigens), that can be regarded as foreign antigens and elicit anti-tumor immune responses in cancer patients. Various TAAs or neoantigens expressed in cancer cells have been identified and utilized as targets for cancer vaccines. One approach to elicit tumor-specific immune responses is termed peptide-based cancer vaccination; it involves administrating TAAs or neoantigen-derived peptide for treatment of cancers...
July 2016: International Immunology
Ravikumar Muthuswamy, John M Corman, Kathryn Dahl, Gurkamal S Chatta, Pawel Kalinski
BACKGROUND: Local infiltration of CD8(+) T cells (CTLs) in tumor lesions predicts overall clinical outcomes and the clinical benefit of cancer patients from immune checkpoint blockade. In the current study, we evaluated local production of different classes of chemokines in prostate cancer lesions, and the feasibility of their modulation to promote selective entry of CTLs into prostate tumors. METHODS: Chemokine expression in prostate cancer lesion was analyzed by TaqMan-based quantitative PCR, confocal fluorescence microscopy and ELISA...
September 2016: Prostate
Jonathan M Carlson, Victor Y Du, Nico Pfeifer, Anju Bansal, Vincent Y F Tan, Karen Power, Chanson J Brumme, Anat Kreimer, Charles E DeZiel, Nicolo Fusi, Malinda Schaefer, Mark A Brockman, Jill Gilmour, Matt A Price, William Kilembe, Richard Haubrich, Mina John, Simon Mallal, Roger Shapiro, John Frater, P Richard Harrigan, Thumbi Ndung'u, Susan Allen, David Heckerman, John Sidney, Todd M Allen, Philip J R Goulder, Zabrina L Brumme, Eric Hunter, Paul A Goepfert
Human leukocyte antigen class I (HLA)-restricted CD8(+) T lymphocyte (CTL) responses are crucial to HIV-1 control. Although HIV can evade these responses, the longer-term impact of viral escape mutants remains unclear, as these variants can also reduce intrinsic viral fitness. To address this, we here developed a metric to determine the degree of HIV adaptation to an HLA profile. We demonstrate that transmission of viruses that are pre-adapted to the HLA molecules expressed in the recipient is associated with impaired immunogenicity, elevated viral load and accelerated CD4(+) T cell decline...
June 2016: Nature Medicine
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