Search results for " alpha-beta"
showing 10 items of 64 documents
Donor interleukin-22 and host type I interferon signaling pathway participate in intestinal graft-versus-host disease via STAT1 activation and CXCL10.
2014
Acute graft-versus-host disease (aGVHD) remains a major complication following allogeneic hematopoietic cell transplantation, limiting the success of this therapy. We previously reported that interleukin-22 (IL-22) participates to aGVHD development, but the underlying mechanisms of its contribution remain poorly understood. In this study, we analyzed the mechanism of the pathological function of IL-22 in intestinal aGVHD. Ex-vivo colon culture experiments indicated that IL-22 was able to induce Th1-like inflammation via signal transducer and activator of transcription factor-1 (STAT1) and CXCL10 induction in the presence of type I interferon (IFN). To evaluate a potential synergy between IL…
Myeloid Cells Restrict MCMV and Drive Stress- Induced Extramedullary Hematopoiesis through STAT1
2019
Cytomegalovirus (CMV) has a high prevalence worldwide, is often fatal for immunocompromised patients, and causes bone marrow suppression. Deficiency of signal transducer and activator of transcription 1 (STAT1) results in severely impaired antiviral immunity. We have used cell- type restricted deletion of Stat1 to determine the importance of myeloid cell activity for the defense against murine CMV (MCMV). We show that myeloid STAT1 limits MCMV burden and infection- associated pathology in the spleen but does not affect ultimate clearance of infection. Unexpectedly, we found an essential role of myeloid STAT1 in the induction of extramedullary hematopoiesis (EMH). The EMH- promoting function…
Decrease in αβ/γδ T-cell ratio is accompanied by a reduction in high-fat diet-induced weight gain, insulin resistance, and inflammation.
2018
The implication of αβ and γδ T cells in obesity-associated inflammation and insulin resistance (IR) remains uncertain. Mice lacking γδ T cells show either no difference or a decrease in high-fat diet (HFD)-induced IR, whereas partial depletion in γδ T cells does not protect from HFD-induced IR. αβ T-cell deficiency leads to a decrease in white adipose tissue (WAT) inflammation and IR without weight change, but partial depletion of these cells has not been studied. We previously described a mouse model overexpressing peroxisome proliferator-activated receptor β (PPAR-β) specifically in T cells [transgenic (Tg) T-PPAR-β] that exhibits a partial depletion in αβ T cells and no change in γδ T-ce…
The actin remodeling protein cofilin is crucial for thymic αβ but not γδ T-cell development
2018
Cofilin is an essential actin remodeling protein promoting depolymerization and severing of actin filaments. To address the relevance of cofilin for the development and function of T cells in vivo, we generated knock-in mice in which T-cell–specific nonfunctional (nf) cofilin was expressed instead of wild-type (WT) cofilin. Nf cofilin mice lacked peripheral αβ T cells and showed a severe thymus atrophy. This was caused by an early developmental arrest of thymocytes at the double negative (DN) stage. Importantly, even though DN thymocytes expressed the TCRβ chain intracellularly, they completely lacked TCRβ surface expression. In contrast, nf cofilin mice possessed normal numbers of γδ T cel…
Human CD4 T-Cells With a Naive Phenotype Produce Multiple Cytokines During Mycobacterium Tuberculosis Infection and Correlate With Active Disease
2018
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…
Highly protective in vivo function of cytomegalovirus IE1 epitope-specific memory CD8 T cells purified by T-cell receptor-based cell sorting.
2005
ABSTRACTReconstitution of antiviral CD8 T cells is essential for controlling cytomegalovirus (CMV) infection after bone marrow transplantation. Accordingly, polyclonal CD8 T cells derived from BALB/c mice infected with murine CMV protect immunocompromised adoptive transfer recipients against CMV disease. The protective population comprises CD8 T cells with T-cell receptors (TCRs) specific for defined and for as-yet-unknown viral epitopes, as well as a majority of nonprotective cells with unrelated specificities. Defined epitopes include IE1/m123 and m164, which are immunodominant in terms of the magnitude of the CD8 T-cell response, and a panel of subordinate epitopes (m04, m18, M45, M83, a…
Values for αβ and γδ T-lymphocytes and CD4+, CD8+, and CD56+ subsets in healthy adult subjects: Assessment by age and gender
2012
Background: Normal reference values in healthy subjects for T-lymphocytes for both types of receptors, αβ and γδ, and their subsets are yet to be defined. The aim of this study was to measure peripheral blood αβ and γδ total T-lymphocytes and their subsets in a population of healthy subjects, in order to obtain valid reference values for studies in human pathology. Methods: We studied a total of 157 healthy subjects, 78 men and 79 women, establishing their levels of CD3+, CD4+, CD8+, CD56+, αβCD3+, αβCD3+CD4+, αβCD3+CD8+, αβCD3+CD56+, γδCD3+, γδCD3+CD4−CD8−, γδCD3+CD8+, and γδCD3+CD56+ T-cells by flow cytometry. The T-cell subsets were compared for different age and gender groups. Results: …
Lysis of human pancreatic adenocarcinoma cells by autologous HLA-class I-restricted cytolytic T-lymphocyte (CTL) clones.
1993
From the primary site of a pancreatic adenocarcinoma (patient BE) a permanent cell line (MZ-PC-2) was established in tissue culture. In the course of mixed lymphocyte-tumor-cell cultures (MLTC) with autologous blood-derived lymphocytes, we isolated CTL clones that lysed autologous tumor cells but not autologous EBV-transformed B cells (EBV-B) and not K562. Pre-treatment of MZ-PC-2 cells with IFN-gamma was required to obtain significant lysis in 4-hr cytotoxicity assays. IFN-gamma was superior to IFN-alpha in that respect. Among MLTC responder lymphocytes, tumor-reactive CTL proliferated more strongly in response to MZ-PC-2 cells treated with IFN-gamma than to untreated tumor cells. Three CT…
MHC-unrestricted recognition of bacteria-infected target cells by human CD8+ cytotoxic T lymphocytes.
1992
Abstract A CD8 + αβTCR + T cell clone (A35) was isolated from the synovial fluid of a patient with postenteric reactive arthritis caused by Yersinia enterocolitica . This clone efficiently killed autologous and allogeneic target cells that had been preincubated with live but not with heat-killed bacteria. There was no restriction by polymorphic parts of HLA-A, -B. or -C molecules and a HLA class II-deficient mutant cell line was lysed as efficiently as its normal counterpart, whereas infected HLA class I-deficient cells (Daudi cells) were not. The clone showed crossreaction between Yersinia enterocolitica , Escherichia coli , Pseudomonas aeruginosa , and Streptococcus pyogenes , but did not…
The influence of major histocompatibility complex class II genes and T-cell Vbeta repertoire on response to immunization with HBsAg.
1998
Nonresponsiveness to HBsAg vaccination is observed in 5-10% of vaccine recipients and is possibly caused by a defect in the T helper cell compartment. The immune response to HBsAg is influenced by genes of the major histocompatibility complex. We have investigated MHC class I and class II antigens in 53 adult responders and 73 nonresponders. Results obtained in this first study were tested in a second study with 56 responders and 62 nonresponders from an infant vaccination trial. In addition, the peripheral Vbeta-chain T-cell receptor repertoire was investigated using monoclonal antibodies and flow-cytometry in 26 adult responders and 38 nonresponders. As previously reported, nonresponsiven…