1. Transcriptional profiles reveal a stepwise developmental program of memory CD8(+) T cell differentiation.

    Vaccine 33(7):914 (2015) PMID 25446821

    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...
  2. Individual T helper cells have a quantitative cytokine memory.

    Immunity 42(1):108 (2015) PMID 25607461

    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...
  3. The alarmin IL-33 promotes regulatory T-cell function in the intestine.

    Nature 513(7519):564 (2014) PMID 25043027

    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...
  4. The alarmin IL-33 promotes regulatory T-cell function in the intestine.

    Nature 513(7519):564 (2014) PMID 25043027 PMCID PMC4339042

    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...
  5. 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) PMID 23976880 PMCID PMC3747991

    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...
  6. Tolerance induction with T cell-dependent protein antigens induces regulatory sialylated IgGs.

    Journal of Allergy and Clinical Immunology 129(6):1647 (2012) PMID 22502800

    Under inflammatory conditions, T cell-dependent (TD) protein antigens induce proinflammatory T- and B-cell responses. In contrast, tolerance induction by TD antigens without costimulation triggers the development of regulatory T cells. Under both conditions, IgG antibodies are generated, but whe...
  7. Tolerance induction with T cell–dependent protein antigens induces regulatory sialylated IgGs

    Journal of Allergy and Clinical Immunology 129(6):1647 (2012)

    Background Under inflammatory conditions, T cell–dependent (TD) protein antigens induce proinflammatory T- and B-cell responses. In contrast, tolerance induction by TD antigens without costimulation triggers the development of regulatory T cells. Under both conditions, IgG an...
  8. The alarmin interleukin-33 drives protective antiviral CD8⁺ T cell responses.

    Science 335(6071):984 (2012) PMID 22323740

    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...
  9. Viral replicative capacity is the primary determinant of lymphocytic choriomeningitis virus persistence and immunosuppression.

    PNAS 107(50):21641 (2010) PMID 21098292 PMCID PMC3003068

    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...
  10. Development of replication-defective lymphocytic choriomeningitis virus vectors for the induction of potent CD8+ T cell immunity.

    Nature Medicine 16(3):339 (2010) PMID 20139992 PMCID PMC3247638

    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...
  11. 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) PMID 20079668

    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...
  12. 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-p...
  13. Professional memory CD4+ T lymphocytes preferentially reside and rest in the bone marrow.

    Immunity 30(5):721 (2009) PMID 19427242

    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 ...
  14. Impaired antibody response causes persistence of prototypic T cell-contained virus.

    PLoS Biology 7(4):e1000080 (2009) PMID 19355789 PMCID PMC2672599

    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...
  15. 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 α2. Antige...
  16. Autoregulation of Th1-mediated inflammation by twist1.

    Journal of Experimental Medicine 205(8):1889 (2008) PMID 18663125 PMCID PMC2525589

    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 (...
  17. Aggravation of viral hepatitis by platelet-derived serotonin.

    Nature Medicine 14(7):756 (2008) PMID 18516052

    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...
  18. 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) PMID 18195073 PMCID PMC2234365

    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...
  19. Extralymphatic virus sanctuaries as a consequence of potent T-cell activation.

    Nature Medicine 13(11):1316 (2007) PMID 17982463

    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...
  20. "Negative vaccination" by specific CD4 T cell tolerisation enhances virus-specific protective antibody responses.

    PLoS ONE 2(11):e1162 (2007) PMID 18000535 PMCID PMC2048666

    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...