Antigen-independent cooperation between T and B lymphocytes is demonstrated in vitro two different experimental protocols: (a) cells from A/J mice immunized vivo either with Group A streptococcal vaccine (Strep A) or the IgG1 fraction of guinea pig anti-idiotypic antibody to A5A idiotype, mature into plaque-forming (PFC) specificity for carbohydrate (A-CHO) during a 4-day culture together idiotypic antibody. (b) Strep.A generate PFC specific A-CHO when cultured presence small concentrations...

Abstract We studied the activation of small resting mouse T lymphocytes by antibodies to cell antigen receptor in combination with other surface antigens. Solid‐phase but not soluble KJ16‐133 and F23.1, both directed β chains V 8 family, activate cells proliferate presence growth factors, a dose‐dependent fashion. Antibodies Lyt‐2 L3T4 had no activating effect at any concentration. However, submitogenic concentrations F23.1 synergized wide range anti‐Lyt‐2 anti‐L3T4 cause proliferation...

A limiting-dilution system is described that makes use of T cell growth factor expansion and allows the determination precursor frequencies for various regulatory effector cells in nonimmune, polyclonally, or specifically activated populations. Two different sets, a frequent rare set, helper precursors with specificity trinitrophenyl-group streptococcal vaccine, could be identified: set Lyt-123 phenotype, present at from 1/1,000 to 1/6,000 splenic cells. It only active low numbers, whereas...

The pathogenesis of chronic inflammatory joint diseases such as adult and juvenile rheumatoid arthritis Lyme is still poorly understood. Central to the various hypotheses in this respect notable involvement T B cells. Here we develop premise that nominal antigen-independent, polyclonal activation preactivated cells via Toll-like receptor (TLR)-2 has a pivotal role initiation perpetuation pathogen-induced disease. We support with following evidence. Both naive effector express TLR-2. A...

// Mohamed Ali Mosrati 1 , Kerstin Willander 2 Ingrid Jakobsen Falk 3 Monica Hermanson 4 Martin Höglund 5 Dick Stockelberg 6 Yuan Wei Kourosh Lotfi 3, 7 Peter Söderkvist Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden Haematology Medical Health Sciences, Immunology, Genetics Pathology, Rudbeck Laboratory, Uppsala Uppsala, Division Hematology, Section for Hematology Coagulation, Internal Sahlgrenska University Hospital, Gothenburg,...

Background: Anemia is a risk factor for worse intracerebral hemorrhage (ICH) outcomes, yet the underlying drivers remain unclear. Though anemia and inflammation are interrelated, it unknown whether influences inflammatory responses to ICH. We investigated impact of on cell phenotypes seen in murine brains with without Methods: Two different models were generated from 8-week-old, female C57/BL6 mice. The separate cohorts included: 1) chronic model via iron-deficient chow compared iron replete...

The isocitrate dehydrogenase (IDH1/IDH2) genes are metabolic enzymes, which frequently mutated in acute myeloid leukemia (AML). enzymes acquire neomorphic enzymatic activity when they mutated.We have investigated the frequency and outcome of acquired IDH1/IDH2 mutations IDH1 SNP 105C > T (rs11554137) 189 unselected de novo AML patients by polymerase chain reaction amplification followed direct sequencing. survival presented Kaplan Meier curves with log rank test. Multivariable analysis was...

De novo acute myeloid leukemia with normal karyotype (NK-AML) comprises a large group of patients no common cytogenetic alterations and variation in treatment response. Single-nucleotide polymorphisms (SNPs) genes related to the metabolism nucleoside analogue AraC, backbone AML treatment, might affect drug sensitivity outcome. Therefore, SNPs may serve as prognostic biomarkers aiding clinicians individualized decisions, aim improving patient outcomes. We analyzed encoding cytidine deaminase...

After productive rearrangement of a TCR beta chain gene, CD4-8- double negative (DN) thymocytes express polypeptide chains on the cell surface together with pre-T alpha and CD3 complex forming pre-TCR. Signals transmitted through pre-TCR select + DN for further maturation to CD4+8+ positive stage, whereas cells that fail generate gene do not continue in development. This process is termed selection. Although it likely differences between proliferation dynamics beta-cells may play role, exact...

Pre-TCR/CD3 signals are essential for survival and maturation of (CD44–25+) DN3 thymocytes via the (CD44–25–) DN4 stage to CD4+CD8+ (DP) cells, a process termed β-selection. The exact developmental stages apoptosis resulting from lack pre-TCR/CD3 have so far not been determined. Here we analyzed apoptotic cell death in relation expression clonotypic TCR polypeptides cycle status immature thymocyte subpopulations wild type (wt) mice several strains with compromised signaling complexes. In wt...

Background Polymorphisms in ABCB1 have the ability to affect both function and expression of transporter protein P-glycoprotein may lead an altered response for many drugs including some antidepressants antipsychotics. Objective The aim this study was examine impact polymorphisms 1199G>A, 1236C>T, 2677G>T/A, 3435C>T deaths by suicide. Patients methods A total 998 consecutive Swedish forensic autopsies performed 2008 individuals 18 years age or older, where femoral blood available a...

Abstract Background TP 53 is commonly mutated in several cancers and confers treatment resistance poor prognosis. Altered expression of mouse double minute 2 ( MDM 2), a negative regulator p53, may also attenuate normal p53 signaling, thereby enhancing tumor transformation to apoptosis. The single nucleotide polymorphism SNP ) 309 has been reported increase impair response. Experimental design We investigated the frequency impact mutations mut) SNP309 on outcome overall survival OS 189 S...

The thiopurines, 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG), are used in the treatment of leukemia. Incorporation deoxythioguanosine nucleotides (dG(s)) into DNA thiopurine-treated cells causes cell death, but there is also evidence that thiopurine metabolites, particularly 6-MP metabolite methylthioinosine monophosphate (MeTIMP), inhibit de novo purine synthesis (DNPS). toxicity DNPS inhibitors influenced by methylthioadenosine phosphorylase (MTAP), a gene frequently deleted cancers....

Despite therapeutic advances, patients with multiple myeloma (MM) continue to experience disease relapse and treatment resistance. The gene ABCB1 encodes the drug transporter P-glycoprotein, which confers resistance through extrusion across cell membrane. Lenalidomide (Len) is excreted mainly via kidneys, and, given expression of P-gp in renal tubuli, single-nucleotide polymorphisms (SNPs) may influence Len plasma concentrations subsequently, outcome treatment. We, therefore, investigated...

Abstract The standard chemotherapy for ovarian cancer is paclitaxel/carboplatin. Patients often exhibit myelosuppressive toxicity, and the treatment response varies considerably. In this study, we investigated previously reported SNP s 1199G>A (rs2229109), 1236C>T (rs1128503), 2677G>T/A (rs2032582), 3435C>T (rs1045642) in ABCB 1 , 1196A>G (rs10509681) CYP 2C8 their association with treatment‐induced myelosuppression, progression‐free survival ( PFS ) overall OS ). From phase...

Summary Drug resistance is a clinically relevant problem in the treatment of acute myeloid leukaemia ( AML ). We have previously reported relationship between single nucleotide polymorphisms SNP s) ABCB 1 , encoding multi‐drug transporter P‐glycoprotein, and overall survival OS ) normal karyotype NK )‐ . Here we extended this material, enabling subgroup analysis based on FLT 3 NPM status, to further elucidate influence s. De novo ‐ patients n = 201) were analysed for 1199G>A, 1236C>T,...

Abstract Fentanyl analogs represent an important group of new psychoactive substances and knowing their efficacy potency might assist in interpreting observed concentrations. The fentanyl can be estimated from vitro studies used to establish structure–activity relationships. In this study, recombinant CHO‐K1 cells (AequoScreen) expressing the human μ‐opioid receptor were dose–response curves via luminescent analysis for cyclopropyl‐, cyclobutyl‐, cyclopentyl‐, cyclohexyl‐,...

During αβ thymocyte development, the clonotypic αβ–T cell receptor (TCR) is preceded by sequentially expressed immature versions of TCR–CD3 complex: pre-TCR, containing a TCR-β chain and invariant pre-Tα, on pre-T cells before rearrangement TCR-α locus. Moreover, clonotype-independent CD3 complexes (CIC) appear pro-T VDJ rearrangements genes. The pre-TCR known to mediate selection, prerequisite for maturation CD4−8− double negative (DN) thymocytes CD4+8+ positive stage. A developmental...

Abstract Thymocytes of mice deficient in the recombinase-activating gene (RAG)-1 or RAG-2 cannot express and receive signals through pre-TCR. As a result, thymocyte development these terminates at CD4/8 double negative (DN), IL-2R-alpha-positive stage. Nevertheless, RAG-deficient DN thymocytes functional CD3 complexes can therefore be induced by anti-CD3 epsilon mAb to mature CD4+8+ positive In present paper we demonstrate that peripheral lymphoid organs (lymph nodes, spleen) blood harbor an...

CD8 is a heterodimeric membrane glycoprotein on MHC class I-restricted T lymphocytes that cooperates with the alpha beta CD3 TCR in recognition of I molecules presenting antigenic peptides. Co-operation has two components: enhancement affinity MHC/peptide-TCR interaction, and signal transduction through cell membrane. The cytolytic function CTL primarily dependent affinity-enhancement component CD8-TCR cooperation whereas activation resting CD8+ cells transmembrane signaling. Using panel...

Abstract Development of αβ and γδ T cells depends on productive rearrangement the appropriate TCR genes their subsequent expression as proteins. TCRβ TCRγδ proteins first appear in DN3 DN4 thymocytes, respectively. So far, it is not clear whether this due to a delayed or more rapid progression thymocytes expressing TCRγδ. The answer question bears distinction between instructive stochastic models αβ/γδ lineage decision. To study question, we monitored initial protein wild-type transgenic...