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[PMID]: 28832948 [Au] Autor: Köhnke T; Wittmann VK; Bücklein VL; Lichtenegger F; Pasalic Z; Hiddemann W; Spiekermann K; Subklewe M [Ad] Endereço: Department of Medicine III, University Hospital, LMU Munich, Munich, Germany. [Ti] Título: Diagnosis of CLL revisited: increased specificity by a modified five-marker scoring system including CD200. [So] Source: Br J Haematol;179(3):480-487, 2017 Nov. [Is] ISSN: 1365-2141 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: The modified Matutes score has been the basis for the diagnosis of chronic lymphocytic leukaemia (CLL) by flow cytometry for the past 15 years. To increase the specificity of the current score we systematically evaluated the diagnostic value of established as well as novel markers, such as CD200, in a large cohort of patients with untreated B-cell malignancies (n = 370). Double positivity for CD5 and CD23 was of very high value to differentiate between CLL and non-CLL cases. In addition, lack of FMC7 expression as well as CD79b expression intensity showed high sensitivity (90·4% and 92·3%) with acceptable specificity (74·4% and 76·9%). For surface IgM, low or absent expression displayed poor specificity in distinguishing CLL from non-CLL cases (51,3%; sensitivity 83,7%). Finally, CD200 positivity showed high sensitivity and specificity. Therefore, CD5/CD23, FMC7, CD79b and CD200 were included in our new CLLflow score, which retained high sensitivity (97·1% vs. 98·6% for the Matutes score, P = 0·38), but showed markedly increased specificity (87·2% vs. 53·8%, P < 0·001). These results were confirmed in our validation cohort (sensitivity 97·0% vs. 100%, P = not applicable; specificity 86·4% vs. 59·1%, P = 0·03). Our data support the use of our new CLLflow score for the diagnosis of CLL with significantly higher specificity. [Mh] Termos MeSH primário: Antígenos CD/sangue Biomarcadores Tumorais/sangue Leucemia Linfocítica Crônica de Células B/diagnóstico [Mh] Termos MeSH secundário: Antígenos CD5/sangue Antígenos CD79/sangue Diagnóstico Diferencial Glicoproteínas/sangue Seres Humanos Imunoglobulina M/sangue Imunofenotipagem Receptores de IgE/sangue Sensibilidade e Especificidade [Pt] Tipo de publicação: EVALUATION STUDIES; JOURNAL ARTICLE [Nm] Nome de substância: 0 (Antigens, CD); 0 (Biomarkers, Tumor); 0 (CD5 Antigens); 0 (CD79 Antigens); 0 (CD79B protein, human); 0 (FMC7 protein, human); 0 (Glycoproteins); 0 (Immunoglobulin M); 0 (Receptors, IgE); 0 (antigens, CD200) [Em] Mês de entrada: 1710 [Cu] Atualização por classe: 171116 [Lr] Data última revisão: 171116 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170824 [St] Status: MEDLINE [do] DOI: 10.1111/bjh.14901

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[PMID]: 28659353 [Au] Autor: Dong M; Artusa P; Kelly SA; Fournier M; Baldwin TA; Mandl JN; Melichar HJ [Ad] Endereço: Maisonneuve-Rosemont Hospital Research Center, Montreal, Quebec H1T 2M4, Canada. [Ti] Título: Alterations in the Thymic Selection Threshold Skew the Self-Reactivity of the TCR Repertoire in Neonates. [So] Source: J Immunol;199(3):965-973, 2017 Aug 01. [Is] ISSN: 1550-6606 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Neonatal and adult T cells differ in their effector functions. Although it is known that cell-intrinsic differences in mature T cells contribute to this phenomenon, the factors involved remain unclear. Given emerging evidence that the binding strength of a TCR for self-peptide presented by MHC (self-pMHC) impacts T cell function, we sought to determine whether altered thymic selection influences the self-reactivity of the TCR repertoire during ontogeny. We found that conventional and regulatory T cell subsets in the thymus of neonates and young mice expressed higher levels of cell surface CD5, a surrogate marker for TCR avidity for self-pMHC, as compared with their adult counterparts, and this difference in self-reactivity was independent of the germline bias of the neonatal TCR repertoire. The increased binding strength of the TCR repertoire for self-pMHC in neonates was not solely due to reported defects in clonal deletion. Rather, our data suggest that thymic selection is altered in young mice such that thymocytes bearing TCRs with low affinity for self-peptide are not efficiently selected into the neonatal repertoire, and stronger TCR signals accompany both conventional and regulatory T cell selection. Importantly, the distinct levels of T cell self-reactivity reflect physiologically relevant differences based on the preferential expansion of T cells from young mice to fill a lymphopenic environment. Therefore, differences in thymic selection in young versus adult mice skew the TCR repertoire, and the relatively higher self-reactivity of the T cell pool may contribute to the distinct immune responses observed in neonates. [Mh] Termos MeSH primário: Receptores de Antígenos de Linfócitos T/imunologia Receptores de Antígenos de Linfócitos T/metabolismo Timócitos/imunologia [Mh] Termos MeSH secundário: Adulto Envelhecimento Animais Animais Recém-Nascidos Antígenos CD5/genética Antígenos CD5/imunologia Diferenciação Celular Seleção Clonal Mediada por Antígeno Sangue Fetal Seres Humanos Recém-Nascido Ativação Linfocitária Camundongos Ligação Proteica Tolerância a Antígenos Próprios Transdução de Sinais Subpopulações de Linfócitos T/imunologia Linfócitos T Reguladores/imunologia Timo/imunologia [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (CD5 Antigens); 0 (Cd5 protein, mouse); 0 (Receptors, Antigen, T-Cell) [Em] Mês de entrada: 1710 [Cu] Atualização por classe: 171116 [Lr] Data última revisão: 171116 [Sb] Subgrupo de revista: AIM; IM [Da] Data de entrada para processamento: 170630 [St] Status: MEDLINE [do] DOI: 10.4049/jimmunol.1602137

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[PMID]: 28562659 [Au] Autor: Freitas CMT; Hamblin GJ; Raymond CM; Weber KS [Ad] Endereço: Department of Microbiology & Molecular Biology, Brigham Young University, Provo, Utah, United States of America. [Ti] Título: Naïve helper T cells with high CD5 expression have increased calcium signaling. [So] Source: PLoS One;12(5):e0178799, 2017. [Is] ISSN: 1932-6203 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: The adaptive immune response is orchestrated by T helper cells and their function is dependent upon interactions between the T cell receptor (TCR), peptide MHC (pMHC) and co-receptors. TCR-pMHC interactions initiate calcium signaling cascades which determine T cell activation, survival, proliferation and differentiation. CD5 is a co-receptor that plays an important role in regulating T cell signaling and fate during thymocyte education. CD5 surface expression on mature single positive thymocytes correlates with the TCR signal strength for positive selecting self-ligands. CD5 also plays a role in T cell function after thymic development is complete. Peripheral T cells with higher CD5 expression respond better to foreign antigen than those with lower CD5 expression and CD5-high T cells are enriched in memory populations. In our study, we examined the role of CD5 expression and calcium signaling in the primary response of T cells using two Listeria monocytogenes specific T helper cells (LLO118 and LLO56). These T cells recognize the same immunodominant epitope (LLO190-205) of L. monocytogenes and have divergent primary and secondary responses and different levels of CD5 expression. We found that each T cell has unique calcium mobilization in response to in vitro stimulation with LLO190-205 and that CD5 expression levels in these cells changed over time following stimulation. LLO56 naïve T helper cells, which expresses higher levels of CD5, have higher calcium mobilization than naïve LLO118 T cells. Three days after in vitro stimulation, LLO118 T cells had more robust calcium mobilization than LLO56 and there were no differences in calcium mobilization 8 days after in vitro stimulation. To further evaluate the role of CD5, we measured calcium signaling in CD5 knockout LLO118 and LLO56 T cells at these three time points and found that CD5 plays a significant role in promoting the calcium signaling of naïve CD5-high LLO56 T cells. [Mh] Termos MeSH primário: Antígenos CD5/metabolismo Sinalização do Cálcio Linfócitos T Auxiliares-Indutores/metabolismo [Mh] Termos MeSH secundário: Citometria de Fluxo Seres Humanos [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (CD5 Antigens) [Em] Mês de entrada: 1709 [Cu] Atualização por classe: 171116 [Lr] Data última revisão: 171116 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170601 [St] Status: MEDLINE [do] DOI: 10.1371/journal.pone.0178799

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[PMID]: 28505514 [Au] Autor: Wang K; Tao L; Su J; Zhang Y; Zou B; Wang Y; Zou M; Chen N; Lei L; Li X [Ad] Endereço: Laboratory of Anti-inflammatory Immunomodulatory Pharmacology, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, PR China; Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, PR C [Ti] Título: TLR4 supports the expansion of FasL CD5 CD1d regulatory B cells, which decreases in contact hypersensitivity. [So] Source: Mol Immunol;87:188-199, 2017 Jul. [Is] ISSN: 1872-9142 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: Certain B cells termed as "regulatory B cells" (Bregs) can suppress the ongoing immune responses and a splenic CD5 CD1d Breg subset identified earlier was shown to exert its regulatory functions through secretion of IL-10. Though FasL expression is an alternative mechanism of immune suppression used by B cells, little is known about the FasL expressing CD5 CD1d Bregs. In this study, we isolated splenocytes or splenic CD19 B cells and compared the efficiency of toll-like receptor(TLR)4 ligand (lipopolysaccharide) with TLR9 ligand (CpG), anti-CD40 and TLR9 ligand (CpG) plus anti-CD40 on the FasL expression of splenic CD5 CD1d Bregs by flow cytometry. FasL expression in CD5 CD1d B cells was rapidly increased after TLR4 ligation. Intriguingly, anti-CD40 and CpG plus anti-CD40 combinations failed to stimulate FasL expression in CD5 CD1d B cells although the IL-10 production was up-regulated in this subset. In addition, LPS and other B10-cell inducers increased the expression of surface molecules like CD86 and CD25, which are correlated to the regulatory functions of B cells. Furthermore, NF-κB and NF-AT inhibitors decreased the TLR4-activated FasL expression in CD5 CD1d B cells. Then we sorted splenic CD5 CD1d Bregs using flow cytometry and found that TLR4-activated CD5 CD1d Bregs suppressed the proliferation of CFSE-labeled CD4 T cells in vitro, which was partly blocked by anti-FasL antibody. In oxazolone-sensitized mice having contact hypersensitivity, FasL expression in splenic CD5 CD1d B cells was decreased compared to the control group after TLR4 ligation. Our findings suggest that the regulatory function of CD5 CD1d B cells could be partly mediated by Fas-FasL pathway and this FasL expressing CD5 CD1d Bregs might participate in the regulation of inflammatory diseases. [Mh] Termos MeSH primário: Antígenos CD1d/metabolismo Linfócitos B Reguladores/metabolismo Antígenos CD5/metabolismo Dermatite de Contato/metabolismo Proteína Ligante Fas/metabolismo Receptor 4 Toll-Like/metabolismo [Mh] Termos MeSH secundário: Animais Proliferação Celular/fisiologia Células Cultivadas Feminino Inflamação/metabolismo Interleucina-10/metabolismo Camundongos Camundongos Endogâmicos C57BL NF-kappa B/metabolismo Linfócitos T Auxiliares-Indutores/metabolismo [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Antigens, CD1d); 0 (CD1d antigen, mouse); 0 (CD5 Antigens); 0 (Cd5 protein, mouse); 0 (Fas Ligand Protein); 0 (Fasl protein, mouse); 0 (NF-kappa B); 0 (Tlr4 protein, mouse); 0 (Toll-Like Receptor 4); 130068-27-8 (Interleukin-10) [Em] Mês de entrada: 1709 [Cu] Atualização por classe: 171116 [Lr] Data última revisão: 171116 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170516 [St] Status: MEDLINE

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[PMID]: 28504304 [Au] Autor: Vasquez M; Simões I; Consuegra-Fernández M; Aranda F; Lozano F; Berraondo P [Ad] Endereço: Instituto de Investigación Sanitaria de Navarra, Pamplona, Spain. [Ti] Título: Exploiting scavenger receptors in cancer immunotherapy: Lessons from CD5 and SR-B1. [So] Source: Eur J Immunol;47(7):1108-1118, 2017 Jul. [Is] ISSN: 1521-4141 [Cp] País de publicação: Germany [La] Idioma: eng [Ab] Resumo: Scavenger receptors (SRs) are structurally heterogeneous cell surface receptors characterized by their capacity to remove extraneous or modified self-macromolecules from circulation, thus avoiding the accumulation of noxious agents in the extracellular space. This scavenging activity makes SRs important molecules for host defense and homeostasis. In turn, SRs keep the activation of the steady-state immune response in check, and participate as co-receptors in the priming of the effector immune responses when the macromolecules are associated with a threat that might compromise host homeostasis. Therefore, SRs built up sophisticated sensor mechanisms controlling the immune system, which may be exploited to develop novel drugs for cancer immunotherapy. In this review, we focus on the regulation of the anti-tumor immune response by two paradigmatic SRs: the lymphocyte receptor CD5 and the more broadly distributed scavenger receptor class B type 1 (SR-B1). Cancer immunity can be boosted by blockade of SRs working as immune checkpoint inhibitors (CD5) and/or by proper engagement of SRs working as innate danger receptor (SR-B1). Thus, these receptors illustrate both the complexity of targeting SRs in cancer immunotherapy and also the opportunities offered by such an approach. [Mh] Termos MeSH primário: Antígenos CD5/metabolismo Neoplasias/terapia Receptores Depuradores/antagonistas & inibidores Receptores Depuradores/metabolismo Receptores Depuradores Classe B/antagonistas & inibidores Receptores Depuradores Classe B/metabolismo [Mh] Termos MeSH secundário: Animais Antígenos CD5/imunologia Homeostase Seres Humanos Imunoterapia/métodos Camundongos Neoplasias/imunologia Neoplasias/metabolismo [Pt] Tipo de publicação: JOURNAL ARTICLE; REVIEW [Nm] Nome de substância: 0 (CD5 Antigens); 0 (Receptors, Scavenger); 0 (SCARB1 protein, human); 0 (Scavenger Receptors, Class B) [Em] Mês de entrada: 1709 [Cu] Atualização por classe: 171116 [Lr] Data última revisão: 171116 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170516 [St] Status: MEDLINE [do] DOI: 10.1002/eji.201646903

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[PMID]: 28493517 [Au] Autor: Shimono J; Miyoshi H; Kiyasu J; Sato K; Kamimura T; Eto T; Miyagishima T; Nagafuji K; Teshima T; Ohshima K [Ad] Endereço: Department of Pathology, Kurume University, School of Medicine, Kurume, Japan. [Ti] Título: Clinicopathological analysis of primary splenic diffuse large B-cell lymphoma. [So] Source: Br J Haematol;178(5):719-727, 2017 Sep. [Is] ISSN: 1365-2141 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: Splenic infiltration is often seen in diffuse large B-cell lymphoma (DLBCL). However, primary splenic DLBCL is rare and studies on its clinicopathological features are limited. We assessed 66 cases of primary splenic DLBCL and 309 control DLBCL, not otherwise specified. Hepatitis C virus antibody prevalence, B symptoms, poor performance status and CD5 positivity differed significantly between the primary splenic DLBCL and control DLBCL groups. Primary splenic DLBCL cases were classified histopathologically into two groups [white pulp pattern (n = 46), red pulp pattern (n = 20)]. Survival analysis showed no difference in overall survival between the primary splenic DLBCL and the control group, but the former had a more favourable progression-free survival. In the examination of primary splenic DLBCL, the white pulp pattern was statistically associated with a lower performance status (2-4), and a lower CD5 positivity than the red pulp pattern. In the survival analysis, the red pulp pattern demonstrated poorer overall survival. Multivariate analysis of overall survival in primary splenic DLBCL cases identified CD5 positivity as an indicator of poor prognosis. Classifying primary splenic DLBCL into white and red pulp patterns was useful in terms of clinicopathological features and overall survival. [Mh] Termos MeSH primário: Linfoma Difuso de Grandes Células B/patologia Neoplasias Esplênicas/patologia [Mh] Termos MeSH secundário: Idoso Biomarcadores Tumorais/metabolismo Antígenos CD5/metabolismo Estudos de Casos e Controles Feminino Anticorpos Anti-Hepatite C/análise Hepatite C Crônica/complicações Seres Humanos Imunofenotipagem Estimativa de Kaplan-Meier Linfoma Difuso de Grandes Células B/imunologia Linfoma Difuso de Grandes Células B/terapia Linfoma Difuso de Grandes Células B/virologia Masculino Meia-Idade Neoplasias Esplênicas/imunologia Neoplasias Esplênicas/terapia Neoplasias Esplênicas/virologia [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Biomarkers, Tumor); 0 (CD5 Antigens); 0 (Hepatitis C Antibodies) [Em] Mês de entrada: 1710 [Cu] Atualização por classe: 171116 [Lr] Data última revisão: 171116 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170512 [St] Status: MEDLINE [do] DOI: 10.1111/bjh.14736

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[PMID]: 28321095 [Au] Autor: Yamamoto Y; Sumii Y; Shiraishi Y; Ikeuchi K; Yamada H; Niiya D; Shiote Y; Yamamoto K; Imajo K [Ad] Endereço: Department of Hematology and Oncology, Okayama City Hospital. [Ti] Título: Primary adrenal diffuse large B-cell lymphoma positive for CD5 and CD10. [So] Source: Rinsho Ketsueki;58(2):161-164, 2017. [Is] ISSN: 0485-1439 [Cp] País de publicação: Japan [La] Idioma: jpn [Ab] Resumo: A 69-year-old man presented with back pain over the prior few months and was hospitalized because of bilateral adrenal masses and fracture of the left sixth rib. The mass on the right measured 6.5×3.6×7.0 cm, that on the left 8.1×4.8×6.9 cm, on CT. The final diagnosis was CD5- and CD10-positive primary adrenal diffuse large B-cell lymphoma (PA-DLBCL) with rib involvement. After EPOCH therapy accompanied with rituximab and intrathecal treatment, the tumors decreased dramatically. However, he died due to disease progression 8 months after the diagnosis. The prognosis of CD5- and CD10-positive PA-DLBCL may be very poor even with rituximab-containing chemotherapy. [Mh] Termos MeSH primário: Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico Antígenos CD5/imunologia Linfoma Difuso de Grandes Células B/tratamento farmacológico Neprilisina/imunologia Rituximab/uso terapêutico [Mh] Termos MeSH secundário: Idoso Seres Humanos Linfoma Difuso de Grandes Células B/diagnóstico Masculino Resultado do Tratamento [Pt] Tipo de publicação: CASE REPORTS; JOURNAL ARTICLE [Nm] Nome de substância: 0 (CD5 Antigens); 4F4X42SYQ6 (Rituximab); EC 3.4.24.11 (Neprilysin) [Em] Mês de entrada: 1706 [Cu] Atualização por classe: 171116 [Lr] Data última revisão: 171116 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170322 [St] Status: MEDLINE [do] DOI: 10.11406/rinketsu.58.161

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[PMID]: 28159554 [Au] Autor: Aparicio-Siegmund S; Deseke M; Lickert A; Garbers C [Ad] Endereço: Institute of Biochemistry, Kiel University, 24118 Kiel, Germany. [Ti] Título: Trans-signaling of interleukin-6 (IL-6) is mediated by the soluble IL-6 receptor, but not by soluble CD5. [So] Source: Biochem Biophys Res Commun;484(4):808-812, 2017 Mar 18. [Is] ISSN: 1090-2104 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: IL-6 exerts its pleiotropic activities on its target cells via the IL-6 alpha-receptor (IL-6R), which is expressed on a limited number of cell types. IL-6 can further signal via soluble forms of its receptor (sIL-6R), a process that has been termed trans-signaling. Recently, CD5 was described as an alternative alpha-receptor for IL-6 on B cells leading to the phosphorylation of the transcription factor STAT3 via the signal-transducing ß-receptor gp130 in a Jak2-dependent manner. In this study, we sought to investigate whether IL-6 was also able to signal via soluble CD5 (sCD5) analogous to IL-6 trans-signaling. We show that IL-6 indeed binds to sCD5, but that this does not lead to the activation of signal transduction or cell proliferation. Furthermore, sCD5 did also not interfere with IL-6 classic signaling, suggesting that the affinity between the two proteins was too weak to provoke a biological effect. Thus, trans-signaling of IL-6 can only occur via sIL-6R, but not sCD5. [Mh] Termos MeSH primário: Antígenos CD5/química Antígenos CD5/metabolismo Interleucina-6/química Interleucina-6/metabolismo Receptores de Interleucina-6/química Receptores de Interleucina-6/metabolismo [Mh] Termos MeSH secundário: Sítios de Ligação Células Hep G2 Seres Humanos Ligação Proteica Transdução de Sinais/fisiologia Solubilidade [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (CD5 Antigens); 0 (Interleukin-6); 0 (Receptors, Interleukin-6) [Em] Mês de entrada: 1706 [Cu] Atualização por classe: 171120 [Lr] Data última revisão: 171120 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170205 [St] Status: MEDLINE

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[PMID]: 28087664 [Au] Autor: Yin X; Yu H; Jin X; Li J; Guo H; Shi Q; Yin Z; Xu Y; Wang X; Liu R; Wang S; Zhang L [Ad] Endereço: Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China. [Ti] Título: Human Blood CD1c+ Dendritic Cells Encompass CD5high and CD5low Subsets That Differ Significantly in Phenotype, Gene Expression, and Functions. [So] Source: J Immunol;198(4):1553-1564, 2017 Feb 15. [Is] ISSN: 1550-6606 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: There are three major dendritic cell (DC) subsets in both humans and mice, that is, plasmacytoid DCs and two types of conventional DCs (cDCs), cDC1s and cDC2s. cDC2s are important for polarizing CD4 naive T cells into different subsets, including Th1, Th2, Th17, Th22, and regulatory T cells. In mice, cDC2s can be further divided into phenotypically and functionally distinct subgroups. However, subsets of human cDC2s have not been reported. In the present study, we showed that human blood CD1c cDCs (cDC2s) can be further separated into two subpopulations according to their CD5 expression status. Comparative transcriptome analyses showed that the CD5 DCs expressed higher levels of cDC2-specific genes, including IFN regulatory factor 4, which is essential for the cDC2 development and its migration to lymph nodes. In contrast, CD5 DCs preferentially expressed monocyte-related genes, including the lineage-specific transcription factor MAFB. Furthermore, compared with the CD5 subpopulation, the CD5 subpopulation showed stronger migration toward CCL21 and overrepresentation among migratory DCs in lymph nodes. Additionally, the CD5 DCs induced naive T cell proliferation more potently than did the CD5 DCs. Moreover, CD5 DCs induced higher levels of IL-10-, IL-22-, and IL-4-producing T cell formation, whereas CD5 DCs induced higher levels of IFN-γ-producing T cell formation. Thus, we show that human blood CD1c cDC2s encompass two subsets that differ significantly in phenotype, that is, gene expression and functions. We propose that these two subsets of human cDC2s could potentially play contrasting roles in immunity or tolerance. [Mh] Termos MeSH primário: Antígenos CD1/imunologia Antígenos CD5/genética Células Dendríticas/imunologia Células Dendríticas/fisiologia Glicoproteínas/imunologia [Mh] Termos MeSH secundário: Antígenos CD1/genética Células Sanguíneas/imunologia Antígenos CD5/análise Diferenciação Celular/efeitos dos fármacos Quimiocina CCL21/farmacologia Células Dendríticas/classificação Células Dendríticas/efeitos dos fármacos Glicoproteínas/genética Seres Humanos Tolerância Imunológica Fatores Reguladores de Interferon/genética Fatores Reguladores de Interferon/imunologia Interleucina-10/imunologia Interleucina-4/biossíntese Interleucina-4/imunologia Interleucinas/biossíntese Interleucinas/imunologia Ativação Linfocitária Fenótipo Linfócitos T Auxiliares-Indutores/imunologia Linfócitos T Reguladores/imunologia Células Th1/imunologia [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Antigens, CD1); 0 (CCL21 protein, human); 0 (CD1C protein, human); 0 (CD5 Antigens); 0 (Chemokine CCL21); 0 (Glycoproteins); 0 (IL10 protein, human); 0 (Interferon Regulatory Factors); 0 (Interleukins); 0 (interferon regulatory factor-4); 0 (interleukin-22); 130068-27-8 (Interleukin-10); 207137-56-2 (Interleukin-4) [Em] Mês de entrada: 1708 [Cu] Atualização por classe: 171116 [Lr] Data última revisão: 171116 [Sb] Subgrupo de revista: AIM; IM [Da] Data de entrada para processamento: 170115 [St] Status: MEDLINE [do] DOI: 10.4049/jimmunol.1600193

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[PMID]: 28074066 [Au] Autor: Chen KH; Wada M; Pinz KG; Liu H; Lin KW; Jares A; Firor AE; Shuai X; Salman H; Golightly M; Lan F; Senzel L; Leung EL; Jiang X; Ma Y [Ad] Endereço: iCell Gene Therapeutics LLC, Research &Development Division, Long Island High Technology Incubator, Stony Brook, NY, USA. [Ti] Título: Preclinical targeting of aggressive T-cell malignancies using anti-CD5 chimeric antigen receptor. [So] Source: Leukemia;31(10):2151-2160, 2017 Oct. [Is] ISSN: 1476-5551 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: The outlook for T-cell malignancies remain poor due to the lack of effective therapeutic options. Chimeric antigen receptor (CAR) immunotherapy has recently shown promise in clinical trials for B-cell malignancies, however, designing CARs for T-cell based disease remain a challenge due to the shared surface antigen pool between normal and malignant T-cells. Normal T-cells express CD5 but NK (natural killer) cells do not, positioning NK cells as attractive cytotoxicity cells for CD5CAR design. Additionally, CD5 is highly expressed in T-cell acute lymphoblastic leukemia (T-ALL) and peripheral T-cell lymphomas (PTCLs). Here, we report a robust anti-CD5 CAR (CD5CAR) transduced into a human NK cell line NK-92 that can undergo stable expansion ex vivo. We found that CD5CAR NK-92 cells possessed consistent, specific, and potent anti-tumor activity against a variety of T-cell leukemia and lymphoma cell lines as well as primary tumor cells. Furthermore, we were able to demonstrate significant inhibition and control of disease progression in xenograft mouse models of T-ALL. The data suggest that CAR redirected targeting for T-cell malignancies using NK cells may be a viable method for new and complementary therapeutic approaches that could improve the current outcome for patients. [Mh] Termos MeSH primário: Antígenos de Neoplasias/imunologia Antígenos CD5/imunologia Imunoterapia Adotiva/métodos Células Matadoras Naturais/imunologia Linfoma de Células T Periférico/terapia Terapia de Alvo Molecular Leucemia-Linfoma Linfoblástico de Células T Precursoras/terapia Proteínas Recombinantes de Fusão/imunologia [Mh] Termos MeSH secundário: Ligante 4-1BB/genética Ligante 4-1BB/imunologia Animais Antígenos CD28/imunologia Complexo CD3/genética Complexo CD3/imunologia Antígenos CD8/imunologia Linhagem Celular Tumoral Técnicas de Cocultura Citotoxicidade Imunológica Seres Humanos Células Matadoras Naturais/transplante Linfoma de Células T Periférico/patologia Camundongos Leucemia-Linfoma Linfoblástico de Células T Precursoras/patologia Terapia de Salvação Anticorpos de Cadeia Única/genética Anticorpos de Cadeia Única/imunologia Transdução Genética Membro 9 da Superfamília de Receptores de Fatores de Necrose Tumoral/imunologia Ensaios Antitumorais Modelo de Xenoenxerto [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (4-1BB Ligand); 0 (Antigens, Neoplasm); 0 (CD28 Antigens); 0 (CD3 Complex); 0 (CD3 antigen, zeta chain); 0 (CD5 Antigens); 0 (CD8 Antigens); 0 (Recombinant Fusion Proteins); 0 (Single-Chain Antibodies); 0 (TNFRSF9 protein, human); 0 (Tumor Necrosis Factor Receptor Superfamily, Member 9) [Em] Mês de entrada: 1710 [Cu] Atualização por classe: 171116 [Lr] Data última revisão: 171116 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170112 [St] Status: MEDLINE [do] DOI: 10.1038/leu.2017.8

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