Superoxide Dismutase 1 Protects Hepatocytes from Type I Interferon-Driven Oxidative Damage.
Immunity 43(5):974 (2015)
Tissue damage caused by viral hepatitis is a major cause of morbidity and mortality worldwide. Using a mouse model of viral hepatitis, we identified virus-induced early transcriptional changes in the redox pathways in the liver, including downregulation of superoxide dismutase 1 (Sod1). Sod1(-/-...
MICROBIOME. Microbiota RORgulates intestinal suppressor T cells.
Science 349(6251):929 (2015)
Prostaglandin D2 and leukotriene E4 synergize to stimulate diverse TH2 functions and TH2 cell/neutrophil crosstalk.
Journal of Allergy and Clinical Immunology 135(5):1358 (2015)
Prostaglandin D2 (PGD2) and cysteinyl leukotrienes (cysLTs) are lipid mediators derived from mast cells, which activate TH2 cells. The combination of PGD2 and cysLTs (notably cysteinyl leukotriene E4 [LTE4]) enhances TH2 cytokine production. However, the synergistic interaction of cysLTs with PG...
T-bet- and STAT4-dependent IL-33 receptor expression directly promotes antiviral Th1 cell responses.
PNAS 112(13):4056 (2015)
During infection, the release of damage-associated molecular patterns, so-called "alarmins," orchestrates the immune response. The alarmin IL-33 plays a role in a wide range of pathologies. Upon release, IL-33 signals through its receptor ST2, which reportedly is expressed only on CD4(+) T cells...
Transcriptional profiles reveal a stepwise developmental program of memory CD8(+) T cell differentiation.
Vaccine 33(7):914 (2015)
The generation of CD8(+) T-cell memory is a major aim of vaccination. While distinct subsets of CD8(+) T-cells are generated following immunization that differ in their ability to confer long-term immunity against infection, the transcriptional profiles of these subsets within endogenous vaccine...
Individual T helper cells have a quantitative cytokine memory.
Immunity 42(1):108 (2015)
The probabilistic expression of cytokine genes in differentiated T helper (Th) cell populations remains ill defined. By single-cell analyses and mathematical modeling, we show that one stimulation featured stable cytokine nonproducers as well as stable producers with wide cell-to-cell variabilit...
The alarmin IL-33 promotes regulatory T-cell function in the intestine.
Nature 513(7519):564 (2014)
FOXP3(+) regulatory T cells (Treg cells) are abundant in the intestine, where they prevent dysregulated inflammatory responses to self and environmental stimuli. It is now appreciated that Treg cells acquire tissue-specific adaptations that facilitate their survival and function; however, key ho...
Stable T-bet(+)GATA-3(+) Th1/Th2 hybrid cells arise in vivo, can develop directly from naive precursors, and limit immunopathologic inflammation.
PLoS Biology 11(8):e1001633 (2013)
Differentiated T helper (Th) cell lineages are thought to emerge from alternative cell fate decisions. However, recent studies indicated that differentiated Th cells can adopt mixed phenotypes during secondary immunological challenges. Here we show that natural primary immune responses against p...
The alarmin interleukin-33 drives protective antiviral CD8⁺ T cell responses.
Science 335(6071):984 (2012)
Pathogen-associated molecular patterns decisively influence antiviral immune responses, whereas the contribution of endogenous signals of tissue damage, also known as damage-associated molecular patterns or alarmins, remains ill defined. We show that interleukin-33 (IL-33), an alarmin released f...
Viral replicative capacity is the primary determinant of lymphocytic choriomeningitis virus persistence and immunosuppression.
PNAS 107(50):21641 (2010)
The Clone 13 (Cl13) strain of lymphocytic choriomeningitis virus is widely studied as a model of chronic systemic viral infection. Here, we used reverse genetic techniques to identify the molecular basis of Cl13 persistence and immunosuppression, the characteristics differentiating it from the c...
Development of replication-defective lymphocytic choriomeningitis virus vectors for the induction of potent CD8+ T cell immunity.
Nature Medicine 16(3):339 (2010)
Lymphocytic choriomeningitis virus (LCMV) exhibits natural tropism for dendritic cells and represents the prototypic infection that elicits protective CD8(+) T cell (cytotoxic T lymphocyte (CTL)) immunity. Here we have harnessed the immunobiology of this arenavirus for vaccine delivery. By using...
Interferons direct Th2 cell reprogramming to generate a stable GATA-3(+)T-bet(+) cell subset with combined Th2 and Th1 cell functions.
Immunity 32(1):116 (2010)
Current T cell differentiation models invoke separate T helper 2 (Th2) and Th1 cell lineages governed by the lineage-specifying transcription factors GATA-3 and T-bet. However, knowledge on the plasticity of Th2 cell lineage commitment is limited. Here we show that infection with Th1 cell-promot...
Professional memory CD4+ T lymphocytes preferentially reside and rest in the bone marrow.
Immunity 30(5):721 (2009)
CD4(+) T lymphocytes are key to immunological memory. Here we show that in the memory phase of specific immune responses, most of the memory CD4(+) T lymphocytes had relocated into the bone marrow (BM) within 3-8 weeks after their generation-a process involving integrin alpha2. Antigen-specific ...
Impaired antibody response causes persistence of prototypic T cell-contained virus.
PLoS Biology 7(4):e1000080 (2009)
CD8 T cells are recognized key players in control of persistent virus infections, but increasing evidence suggests that assistance from other immune mediators is also needed. Here, we investigated whether specific antibody responses contribute to control of lymphocytic choriomeningitis virus (LC...
Autoregulation of Th1-mediated inflammation by twist1.
Journal of Experimental Medicine 205(8):1889 (2008)
The basic helix-loop-helix transcriptional repressor twist1, as an antagonist of nuclear factor kappaB (NF-kappaB)-dependent cytokine expression, is involved in the regulation of inflammation-induced immunopathology. We show that twist1 is expressed by activated T helper (Th) 1 effector memory (...
Aggravation of viral hepatitis by platelet-derived serotonin.
Nature Medicine 14(7):756 (2008)
More than 500 million people worldwide are persistently infected with hepatitis B virus or hepatitis C virus. Although both viruses are poorly cytopathic, persistence of either virus carries a risk of chronic liver inflammation, potentially resulting in liver steatosis, liver cirrhosis, end-stag...
Long-lived virus-reactive memory T cells generated from purified cytokine-secreting T helper type 1 and type 2 effectors.
Journal of Experimental Medicine 205(1):53 (2008)
Many vaccination strategies and immune cell therapies aim at increasing the numbers of memory T cells reactive to protective antigens. However, the differentiation lineage and therefore the optimal generation conditions of CD4 memory cells remain controversial. Linear and divergent differentiati...
Extralymphatic virus sanctuaries as a consequence of potent T-cell activation.
Nature Medicine 13(11):1316 (2007)
T helper cells can support the functions of CD8(+) T cells against persistently infecting viruses such as murine lymphocytic choriomeningitis virus (LCMV), cytomegalovirus, hepatitis C virus and HIV. These viruses often resist complete elimination and remain detectable at sanctuary sites, such a...
"Negative vaccination" by specific CD4 T cell tolerisation enhances virus-specific protective antibody responses.
PLoS ONE 2(11):e1162 (2007)
Cooperation of CD4+ T helper cells with specific B cells is crucial for protective vaccination against pathogens by inducing long-lived neutralizing antibody responses. During infection with persistence-prone viruses, prolonged virus replication correlates with low neutralizing antibody response...
Cytogenetic characterization of a BCR-ABL transduced mouse cell line.
Cancer Genetics and Cytogenetics 161(1):51 (2005)
Most patients with Philadelphia (Ph)-positive acute lymphoblastic leukemia (ALL) show evidence of secondary chromosome aberrations that may influence the course of disease and response to treatment. To better understand how these secondary chromosomal aberrations occur and to investigate whether...