E. Teixeiro - Academia.edu (original) (raw)

Papers by E. Teixeiro

ObjectiveWe describe our Fall 2020 study of college students’ COVID-19 related behaviors, attitud... more ObjectiveWe describe our Fall 2020 study of college students’ COVID-19 related behaviors, attitudes, and antibody test results.ParticipantsThe study included 1,446 randomly selected and self-enrolled undergraduate and graduate students from a midwestern university.MethodsAn online survey was distributed to a sample of students, between September and December 2020. A sub-group also participated in a SARS-CoV-2 antibody blood draw.ResultsNearly half of students reported a prior COVID-19 test with 22% indicating a positive test, which represents an 11% positivity rate across all student participants. Of those who participated in antibody testing, 15.1% tested positive for SARS-CoV-2 antibodies. Seventy-seven percent of participants said they would get vaccinated. One-third of students reported moderate to severe generalized anxiety disorder and 13% reported moderate to severe depression.ConclusionsThis study informed campus decisions in Fall 2020. The importance of effective public hea...

Tracking SARS-CoV-2 genetic diversity is strongly indicated because diversifying selection may le... more Tracking SARS-CoV-2 genetic diversity is strongly indicated because diversifying selection may lead to the emergence of novel variants resistant to naturally acquired or vaccine-induced immunity. To monitor New York City (NYC) for the presence of novel variants, we amplified regions of the SARS-CoV-2 Spike protein gene from RNA acquired from all 14 NYC wastewater treatment plants (WWTPs) and ascertained the diversity of lineages from these samples using high throughput sequencing. Here we report the detection and increasing frequencies of novel SARS-CoV-2 lineages not recognized in GISAID’s EpiCoV database. These lineages contain mutations rarely observed in clinical samples, including Q493K, Q498Y, H519N and T572N. Many of these mutations were found to expand the tropism of SARS-CoV-2 pseudoviruses by allowing infection of cells expressing the human, mouse, or rat ACE2 receptor. In addition, pseudoviruses containing the Spike amino acid sequence of these lineages were found to be r...

Frontiers in Immunology, 2015

T cell memory plays a critical role in our protection against pathogens and tumors. The antigen a... more T cell memory plays a critical role in our protection against pathogens and tumors. The antigen and its interaction with the T cell receptor (TCR) is one of the initiating elements that shape T cell memory together with inflammation and costimulation. Over the last decade, several transcription factors and signaling pathways that support memory programing have been identified. However, how TCR signals regulate them is still poorly understood. Recent studies have shown that the biochemical rules that govern T cell memory, strikingly, change depending on the TCR signal strength. Furthermore, TCR signal strength regulates the input of cytokine signaling, including pro-inflammatory cytokines. These highlight how tailoring antigenic signals can improve immune therapeutics. In this review, we focus on how TCR signaling regulates T cell memory and how the quantity and quality of TCR-peptide-MHC interactions impact the multiple fates a T cell can adopt in the memory pool.

Journal of Histochemistry & Cytochemistry, 2001

The scavenger receptors CLA-1/SR-BI and CD36 interact with native and modified lipoproteins and w... more The scavenger receptors CLA-1/SR-BI and CD36 interact with native and modified lipoproteins and with some anionic phospholipids. In addition, CD36 binds/transports long-chain free fatty acids. Recent biochemical evidences indicates that the rabbit CLA-1/SR-BI receptor can be detected in enterocytes, and previous studies showed the presence of mRNA for both CLA-1/SR-BI and CD36 in some segments of the intestinal tract. These findings prompted us to study their respective localization and distribution from the human stomach to the colorectal segments, using immunohistochemical methods. Their expression in the colorectal carcinoma-derived cell line Caco-2 was analyzed by Northern blotting. In the human intestinal tract, CLA-1/SR-BI was found in the brush-border membrane of enterocytes from the duodenum to the rectum. However, CD36 was found only in the duodenal and jejunal epithelium, whereas enterocytes from other intestinal segments were not stained. In the duodenum and jejunum, CD36...

Immunity, 2000

that formation of the T cell synapse (Grakoui et al., 1999) and assembly of productive signaling ... more that formation of the T cell synapse (Grakoui et al., 1999) and assembly of productive signaling complexes depend on reorganization of the actin cytoskeleton (reviewed in Penninger and Crabtree, 1999) and are regulated, in addition, by specialized lipid microdomains

European Journal of Immunology, 1999

Apoptosis induced through the TCR in CD4 + T cells is mostly mediated by the inducible expression... more Apoptosis induced through the TCR in CD4 + T cells is mostly mediated by the inducible expression of Fas ligand (FasL) as a primary event leading to the commitment to death. To gain a better understanding of the transcriptional events that regulate this expression, we took advantage of our previously described mutant Jurkat cells. These cells are deficient in FasL expression and apoptosis induced upon TCR triggering, although their cytokine (IL-2 and IFN-+) production is normal. Here we show that both a FasL-and a consensus NF-O Breporter construct are inefficiently induced in these cells compared to wild-type cells. In addition, we demonstrate that the inducible transcriptional activity of the FasL reporter is abolished by specific inhibitors of NF-O B activation. Thus, we could trace the deficit of the mutant cells to an inefficient NF-O B activation, evidencing a relevant role for NF-O B in the regulation of FasL expression in activated T cells. Furthermore, our results suggest that the induction of FasL versus cytokine gene expression is differentially sensitive to NF-O B deprivation.

Science, 2009

Following infection, naïve CD8 + T cells bearing pathogen-specific T cell receptors (TCRs) diffe... more Following infection, naïve CD8 + T cells bearing pathogen-specific T cell receptors (TCRs) differentiate into a mixed population of short-lived effector and long-lived memory T cells to mediate an adaptive immune response. How the TCR regulates memory T cell development has remained elusive. Using a mutant TCR transgenic model, we found that point mutations in the TCR β transmembrane domain (βTMD) impair the development and function of CD8 + memory T cells without affecting primary effector T cell responses. Mutant T cells are deficient in polarizing the TCR and in organizing the nuclear factor κB signal at the immunological synapse. Thus, effector and memory states of CD8 + T cells are separable fates, determined by differential TCR signaling.

Journal of immunology (Baltimore, Md. : 1950), May 15, 2016

The scaffold molecule POSH is crucial for the regulation of proliferation and effector function i... more The scaffold molecule POSH is crucial for the regulation of proliferation and effector function in CD8(+) T cells. However, its role in CD4(+) T cells is not known. In this study, we found that disruption of the POSH scaffold complex established a transcriptional profile that strongly skewed differentiation toward Th2, led to decreased survival, and had no effect on cell cycle entry. This is in stark contrast to CD8(+) T cells in which POSH regulates cell cycle and does not affect survival. Disruption of POSH in CD4(+) T cells resulted in the loss of Tak1-dependent activation of JNK1/2 and Tak1-mediated survival. However, in CD8(+) T cells, POSH regulates only JNK1. Remarkably, each type of T cell had a unique composition of the POSH scaffold complex and distinct posttranslational modifications of POSH. These data indicate that the mechanism that regulates POSH function in CD4(+) T cells is different from CD8(+) T cells. All together, these data strongly suggest that POSH is essenti...

Journal of Experimental Medicine, 1998

We have previously shown that a tyrosine to leucine replacement in the transmembrane region of T ... more We have previously shown that a tyrosine to leucine replacement in the transmembrane region of T cell receptor (TCR)-β results in a deficient induction of CD95-L and apoptosis upon TCR triggering in a transfected T cell line. By contrast, interleukin (IL)-2 production and the expression of CD25 and CD69 were normally induced. Since the mutation in TCR-β also resulted in impaired association of CD3-ζ, it was proposed that this chain is specifically required for the induction of apoptosis. We now show that the deficient induction of CD95-L and apoptosis does not derive from a general lower production of second messengers, since intracellular Ca2+ fluxes and tyrosine phosphorylation of total proteins were elicited at wild-type levels. Unlike in T cell clones stimulated with partial agonists, both p21 and p18 forms of tyrosine-phosphorylated CD3-ζ were detected, although the overall level of tyrosine-phosphorylated CD3-ζ was low. More strikingly, inducible association of ZAP70 to CD3-ζ ...

Journal of Biological Chemistry, 2002

The bases that support the versatility of the T cell receptor (TCR) to generate distinct T cell r... more The bases that support the versatility of the T cell receptor (TCR) to generate distinct T cell responses remain unclear. We have previously shown that mutant cells in the transmembrane domain of TCR␤ chain are impaired in TCR-induced apoptosis but are not affected in other functions. Here we describe the biochemical mechanisms by which this mutant receptor supports some T cell responses but fails to induce apoptosis. Extracellular signal-regulated protein kinase (ERK) is activated at higher and more sustained levels in TCR␤mutated than in wild type cells. Conversely, activation of both c-Jun N-terminal kinase and p38 mitogen-activated protein kinase is severely reduced in mutant cells. By attempting to link this unbalanced induction to altered upstream events, we found that ZAP-70 is normally activated. However, although SLP-76 phosphorylation is normally induced, TCR engagement of mutant cells results in lower tyrosine phosphorylation of LAT but in higher tyrosine phosphorylation of Vav than in wild type cells. The results suggest that an altered signaling cascade leading to an imbalance in mitogen-activated protein kinase activities is involved in the selective impairment of apoptosis in these mutant cells. Furthermore, they also provide new insights in the contribution of TCR to decipher the signals that mediate apoptosis distinctly from proliferation.

Immunity, 2004

to several rounds of cell division, proliferating T cells Department of Research become sensitive... more to several rounds of cell division, proliferating T cells Department of Research become sensitive to apoptosis, resulting in activation-University Hospital-Basel induced cell death (AICD) (Boehme and Lenardo, 1993; Hebelstrasse 20 Irmler et al., 1997; Suda et al., 1996). Activated T cells CH-4031 Basel express death-inducing proteins on their surface such Switzerland as Fas ligand (FasL or CD95L) and Fas (CD95) (Ju et al., 2 Ludwig Institute for Cancer Research 1995; Sytwu et al., 1996). The role of this ligand/receptor Lausanne Branch pair has been well documented, since FasL-and Fas-University of Lausanne deficient mice have lymphoproliferative phenotypes 1066 Epalinges (Cohen and Eisenberg, 1991; Russell et al., 1993). More-Switzerland over, the majority of patients suffering from autoimmune 3 Department of Biochemistry lymphoproliferative syndrome (ALPS) have mutations in University of Lausanne either the Fas or FasL genes, pointing to the important Chemin des Boveresses 155 role of this receptor/ligand pair in regulating T cell prolif-CH-1066 Epalinges eration (Rieux-Laucat et al., 1995). Switzerland The expression of FasL is controlled by TCR-gener-4 Department of Immunology ated signals, and the FasL promoter contains binding Fundació n Jimé nez Díaz sites for the transcription factors NF-AT, NF-B, Egr-1, Avda. Reyes Cató licos 2 Egr-2, and Egr-3, Sp-1, AP-1, ATF-2, c-Myc, and FKHRL1 28040 Madrid (Green et al., 2003; Kavurma and Khachigian, 2003). Spain Matsui et al. have demonstrated that after CD3 stimulation, NF-B regulates murine FasL transcription by cooperative interactions with AP-1 and Egr (Matsui et al., Summary 1998, 2000). This, together with other studies, suggests that NF-B is an important factor controlling FasL induc-We have studied the role of the T cell receptor (TCR) tion in T cells (Hsu et al., 1999; Kasibhatla et al., 1999; ␤ chain transmembrane and cytoplasmic domains Teixeiro et al., 1999). (␤TM/Cyto) in T cell signaling. Upon antigen stimula-NF-B is induced by different receptor-generated sigtion, T lymphocytes expressing a TCR with mutant nals that converge by phosphorylating and activating ␤TM and Cyto domains accumulate in large numbers the IKK complex (Rothwarf and Karin, 1999). Recently, and are specifically defective in undergoing activationtwo signaling adaptors, Carma-1 and Bcl-10, have been induced cell death (AICD). The mutant TCR poorly reshown to link the TCR and PKC to the activation of the cruits the protein adaptor Carma-1 and is subse-IKK complex (Gaide et al., 2002; Jun and Goodnow, quently impaired in activating NF-B. This signaling 2003; Pomerantz et al., 2002; Ruland et al., 2001; Wang defect leads to a reduced expression of Fas ligand et al., 2002). Upon TCR engagement, Carma-1 is associ-(FasL) and to a reduction in AICD. These ␤ chain doated with the TCR, allowing the recruitment of Bcl-10 mains are involved in discriminating cell division and to the membrane. This, together with PKC activation, apoptosis. leads to activation of the IKK complex and subsequent phosphorylation and degradation of the NF-B inhibitor IB␣, resulting in NF-B activation (Che et al., 2004;

The Journal of Immunology, 2013