C Nagler-Anderson

Harvard Medical School, Boston, Massachusetts, United States

Are you C Nagler-Anderson?

Claim your profile

Publications (28)219.28 Total impact

  • Cathryn Nagler-Anderson
    Advances in experimental medicine and biology 02/2006; 579:15-23. · 1.83 Impact Factor
  • Cathryn Nagler-Anderson
    [Show abstract] [Hide abstract]
    ABSTRACT: Work from our laboratory has shown that an enteric helminth infection can act as an adjuvant to prime for a Th2-biased response to a typically tolerogenic form of dietary antigen. Helminth infection did not, however, prime for an allergic response. Using a model in which systemic anaphylactic symptoms and antigen specific IgE are induced in C3H/HeJ mice by repeated intragastric administration of peanut antigen with the mucosal adjuvant cholera toxin we showed that an enteric helminth infection protects against the development of food allergy. Helminth-dependent protection against allergy was abrogated when the helminth-infected, allergen-sensitized mice were treated with neutralizing antibodies to IL-10. Recent work from our laboratory and others has implicated helminth induced immunoregulatory cells in protection against allergy. We will discuss the characteristics of the immunoregulatory cell populations that have been described and the mechanism(s) by which they may function in the suppression of allergy.
    Chemical immunology and allergy 02/2006; 90:1-13.
  • Guénolée Prioult, Cathryn Nagler-Anderson
    [Show abstract] [Hide abstract]
    ABSTRACT: Allergic hyperreactivity is defined as an exaggerated immune response [typically immunoglobulin E (IgE) but also non-IgE mediated] toward harmless antigenic stimuli. The prevalence of allergic disease has increased dramatically during the last 20 years, especially in developed countries. Both genetic and environmental factors contribute to susceptibility to allergy. Evidence has emerged supporting the hypothesis that a reduction in antigenic stimulation brought about by widespread vaccination, improvements in standards of hygiene, and extensive use of antibiotics has contributed to the dysregulation of T-helper 2 cell (Th2) type responsiveness that typifies allergy. Regulation of the inherently Th2-biased mucosal immune response is crucial both to the maintenance of homeostasis at this strategic defensive barrier and to the prevention of allergic disease. The ability of Th1 responses to counter-regulate Th2 reactivity is well characterized. More recently, interest has centered on regulatory T cells, which can suppress both Th1 and Th2 cells through the secretion of immunosuppressive cytokines such as interleukin-10 and transforming growth factor-beta. In this review, we discuss the basic cellular mechanisms of allergic diseases at mucosal surfaces, focusing on allergic responses to food, before examining newer work that suggests the induction of allergic hyperreactivity is due to a deficient immunoregulatory network, a lack of microbial stimulation, or both.
    Immunological Reviews 09/2005; 206:204-18. · 12.16 Impact Factor
  • Source
    Donald W Smith, Cathryn Nagler-Anderson
    [Show abstract] [Hide abstract]
    ABSTRACT: The gut-associated lymphoid tissue (GALT) is constantly exposed to a variety of Ags and must therefore decipher a large number of distinct signals at all times. Responding correctly to each set of signals is crucial. When the GALT receives signals from the intestinal flora or food Ags, it must induce a state of nonresponsiveness (mucosal tolerance). In contrast, when pathogenic bacteria invade the intestinal mucosa, it is necessary to elicit strong T and B cell responses. The GALT is therefore in the position of constantly fighting intolerance to food and the commensal flora while effectively battling infectious microbes. Determining precisely which type of response to generate in each case is key to the prevention of immune dysregulation and tissue damage.
    The Journal of Immunology 05/2005; 174(7):3851-7. · 5.52 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The mechanisms by which signaling by the innate immune system controls susceptibility to allergy are poorly understood. In this report, we show that intragastric administration of a food allergen with a mucosal adjuvant induces allergen-specific IgE, elevated plasma histamine levels, and anaphylactic symptoms in three different strains of mice lacking a functional receptor for bacterial LPS (Toll-like receptor 4 (TLR4)), but not in MHC-matched or congenic controls. Susceptibility to allergy correlates with a Th2-biased cytokine response in both the mucosal (mesenteric lymph node and Peyer's patch) and systemic (spleen) tissues of TLR4-mutant or -deficient mice. TLR4-mutant mice are not inherently impaired in their ability to regulate Th1 cytokine production because they respond to stimulation via TLR9. Coadministration of CpG oligodeoxynucleotides during sensitization of TLR4-mutant mice with allergen plus CT abrogates anaphylactic symptoms and Ag-specific IgE, and results in a Th1-polarized cytokine response. When the composition of the bacterial flora is reduced and altered by antibiotic administration (beginning at 2 wk of age), TLR4 wild-type mice become as susceptible to the induction of allergy as their TLR4-mutant counterparts. Both allergen-specific IgE and Th2 cytokine responses are reduced in antibiotic-treated mice in which the flora has been allowed to repopulate. Taken together, our results suggest that TLR4-dependent signals provided by the intestinal commensal flora inhibit the development of allergic responses to food Ags.
    The Journal of Immunology 07/2004; 172(11):6978-87. · 5.52 Impact Factor
  • Source
    Cathryn Nagler-Anderson, Atul K Bhan, Daniel K Podolsky, Cox Terhorst
    Nature Immunology 03/2004; 5(2):119-22. · 26.20 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Although helminths induce a polarized Th2 response they have been shown, in clinical studies, to confer protection against allergies. To elucidate the basis for this paradox, we have examined the influence of an enteric helminth infection on a model of food allergy. Upon Ag challenge, mice fed peanut (PN) extract plus the mucosal adjuvant cholera toxin (CT) produced PN-specific IgE that correlated with systemic anaphylactic symptoms and elevated plasma histamine. PN-specific IgE was not induced in helminth-infected mice fed PN without CT. Moreover, when PN plus CT was fed to helminth-infected mice, both PN-specific IgE and anaphylactic symptoms were greatly diminished. The down-regulation of PN-specific IgE was associated with a marked reduction in the secretion of IL-13 by PN-specific T cells. When helminth-infected PN plus CT-sensitized mice were treated with neutralizing Abs to IL-10, the PN-specific IgE response and anaphylactic symptoms were similar to, or greater than, those seen in mice that receive PN and CT alone. Taken together, these results suggest that helminth-dependent protection against allergic disease involves immunoregulatory mechanisms that block production of allergen-specific IgE.
    The Journal of Immunology 10/2002; 169(6):3284-92. · 5.52 Impact Factor
  • C Nagler-Anderson
    [Show abstract] [Hide abstract]
    ABSTRACT: Immunologists typically study the immune responses induced in the spleen or peripheral lymph nodes after parenteral immunization with antigen and poorly defined experimental adjuvants. However, most antigens enter the body through mucosal surfaces. It is now clear that the microenvironment in these mucosal barriers has a marked influence on the immune response that ultimately ensues. Nowhere is the microenvironment more influential than in the gut-associated lymphoid tissue (GALT). The GALT must constantly distinguish harmless antigens that are present in food or on commensal bacteria from pathogenic assault by microbes. It is perhaps not surprising, then, that the GALT contains more lymphocytes than all of the secondary lymphoid organs combined.
    Nature reviews. Immunology 11/2001; 1(1):59-67. · 33.13 Impact Factor
  • C Nagler-Anderson, C Terhoust, A K Bhan, D K Podolsky
    Trends in Immunology 04/2001; 22(3):120-2. · 9.49 Impact Factor
  • C Nagler-Anderson, H N Shi
    [Show abstract] [Hide abstract]
    ABSTRACT: The presentation of soluble model food antigens to the intestinal immune system typically induces antigen-specific systemic nonresponsiveness. Yet, the gut-associated lymphoid tissue (GALT) must launch an effective attack against potentially invasive pathogens even as it avoids mounting a response to innocuous food antigens. Although the mechanism by which the GALT is able to recognize and respond to these different forms of antigen is not clear, recent studies have shown that, initially, both tolerogenic and immunogenic forms of orally administered antigen elicit transient T-cell activation and proliferation. The unique microenvironment of the GALT plays a central role in determining whether functional T-cell anergy or adaptive immunity is the ultimate response. Administration of model food proteins with adjuvants (microbial products that activate the innate immune system) induces a productive immune response to this normally tolerogenic form of antigen. Recent work from our laboratory has shown that an ongoing enteric infection can itself act as an adjuvant and prime for a response to an orally administered soluble protein antigen.
    Critical Reviews in Immunology 02/2001; 21(1-3):121-31. · 3.38 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Thy-1 dull gamma delta thymocytes constitute an unusual subset of mature TCR gamma delta cells which share with NK T cells the expression of cell surface markers usually associated with activated or memory cells and the simultaneous production of high levels of IL-4 and IFN-gamma upon activation. In DBA / 2 mice, Thy-1 dull gamma delta thymocytes express a restricted repertoire of TCR that are composed of the V1 gene product mainly associated with V6.4 chains exhibiting very limited junctional sequence diversity. In this study we have characterized this gamma delta T cell population in different strains of mice and show that Thy-1 dull gamma delta thymocytes are present in every strain tested, albeit at different frequencies. Moreover IL-4 production by gamma delta thymocytes is mainly confined to the Thy-1 dull population in every strain tested. Finally, the repertoire of TCR expressed by Thy-1 dull gamma delta thymocytes varies in different strain of mice, although a biased expression of Vgamma1 and Vdelta6 chains was observed in all strains studied. However, the extent of junctional diversity of the V1 and V6 chains expressed by Thy-1 dull gamma delta thymocytes varied from oligoclonal in DBA/2 mice to polyclonal in FVB/N mice. Thy-1 dull gamma delta thymocytes from mouse strains such as C3H/HeJ and BALB/c contain cells with diverse Vdelta6(D)Jdelta junctions together with cells with relatively homogeneous Vdelta6(D)Jdelta junctions, similar to those found in DBA/2. Thus, the Thy-1 dull gamma delta population appears to contain two subsets of cells which differ in the diversity of their TCR.
    European Journal of Immunology 02/2001; 31(1):205-14. · 4.97 Impact Factor
  • European Journal of Immunology - EUR J IMMUNOL. 01/2001; 31(1):205-214.
  • Gastroenterology 01/2001; 120(5). · 12.82 Impact Factor
  • Source
    H N Shi, H Y Liu, C Nagler-Anderson
    [Show abstract] [Hide abstract]
    ABSTRACT: Oral administration of soluble protein Ags typically induces Ag-specific systemic nonresponsiveness. However, we have found that feeding a model food protein, OVA, to helminth-infected mice primes for a systemic OVA-specific Th2 response. In this report we show that, in addition to creating a Th2-priming cytokine environment, helminth infection up-regulates costimulatory molecule expression on mucosal, but not peripheral, APCs. To examine the consequences of mucosal infection for the T cell response to orally administered Ag, we adoptively transferred transgenic, OVA-specific, T cells into normal mice. We found that helminth infection enhances the expansion and survival of transgenic T cells induced by Ag feeding. Transfer of 5,6-carboxyfluorescein diacetate succinimidyl ester-labeled donor cells showed that T cell proliferation in response to Ag feeding takes place primarily in the mesenteric lymph nodes. Upon subsequent peripheral exposure to Ag in adjuvant, the proliferative capacity of the transferred transgenic T cells was reduced in noninfected mice that had been fed OVA. Helminth infection abrogated this reduction in proliferative capacity. Our data suggests that enteric infection can act as an adjuvant for the response to dietary Ags and has implications for allergic responses to food and the efficacy of oral vaccination.
    The Journal of Immunology 01/2001; 165(11):6174-82. · 5.52 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Thy-1dull  δ thymocytes constitute an unusual subset of mature TCR δ cells which share with NK T cells the expression of cell surface markers usually associated with activated or memory cells and the simultaneous production of high levels of IL-4 and IFN- upon activation. In DBA / 2 mice, Thy-1dull  δ thymocytes express a restricted repertoire of TCR that are composed of the V1 gene product mainly associated with Vδ6.4 chains exhibiting very limited junctional sequence diversity. In this study we have characterized this  δ T cell population in different strains of mice and show that Thy-1dull  δ thymocytes are present in every strain tested, albeit at different frequencies. Moreover IL-4 production by  δ thymocytes is mainly confined to the Thy-1dull  δ population in every strain tested. Finally, the repertoire of TCR expressed by Thy-1dull  δ thymocytes varies in different strain of mice, although a biased expression of V1 and Vδ6 chains was observed in all strains studied. However, the extent of junctional diversity of the V1 and Vδ6 chains expressed by Thy-1dull  δ thymocytes varied from oligoclonal in DBA / 2 mice to polyclonal in FVB / N mice. Thy-1dull  δ thymocytes from mouse strains such as C3H / HeJ and BALB / c contain cells with diverse Vδ6(D)Jδ junctions together with cells with relatively homogeneous Vδ6(D)Jδ junctions, similar to those found in DBA / 2. Thus, the Thy-1dull  δ population appears to contain two subsets of cells which differ in the diversity of their TCR.
    European Journal of Immunology 12/2000; 31(1):205 - 214. · 4.97 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Helicobacter pylori is causally associated with gastritis and gastric cancer. Some developing countries with a high prevalence of infection have high gastric cancer rates, whereas in others, these rates are low. The progression of helicobacter-induced gastritis and gastric atrophy mediated by type 1 T-helper cells may be modulated by concurrent parasitic infection. Here, in mice with concurrent helminth infection, helicobacter-associated gastric atrophy was reduced considerably despite chronic inflammation and high helicobacter colonization. This correlated with a substantial reduction in mRNA for cytokines and chemokines associated with a gastric inflammatory response of type 1 T-helper cells. Thus, concurrent enteric helminth infection can attenuate gastric atrophy, a premalignant lesion.
    Nature Medicine 04/2000; 6(5):536-542. · 22.86 Impact Factor
  • Gastroenterology 01/2000; 118(4). · 12.82 Impact Factor
  • H N Shi, C Nagler-Anderson
    [Show abstract] [Hide abstract]
    ABSTRACT: Although immunologists typically examine immune responses in peripheral lymphoid tissues, mucosal surfaces are the first sites at which most antigens are encountered. The role of lymphocytes in the gut-associated lymphoid tissue (GALT) in the production of secretory IgA has been well characterized. Although T cells of the GALT are located in areas likely to have a key role in cell-mediated immunity at mucosal surfaces, the ways in which these cells help defend against mucosal infection are only beginning to be understood. This review examines mucosal T-cell responses to enteric infection with bacteria, viruses, and parasites.
    Current Opinion in Gastroenterology 12/1999; 15(6):529-33. · 4.10 Impact Factor
  • Source
    H N Shi, M J Grusby, C Nagler-Anderson
    [Show abstract] [Hide abstract]
    ABSTRACT: Intragastric administration of soluble protein Ags results in peripheral tolerance to the fed Ag. To examine the role of cytokine regulation in the induction of oral tolerance, we fed OVA to mice deficient in Th1 (Stat 4-/-) and Th2 (Stat 6-/-) cells and compared their response to that of normal BALB/c controls. We found that, in spite of these deficiencies, OVA-specific peripheral cell-mediated and humoral nonresponsiveness was maintained in both Stat 4-/- and Stat 6-/- mice. In the mucosa, both Peyer's patch T cell proliferative responses and OVA-specific fecal IgA were reduced in Stat 4-/- and Stat 6-/- mice fed OVA but not in normal BALB/c controls. Mucosal, but not peripheral, nonresponsiveness was abrogated by the inclusion of a neutralizing Ab to TGF-beta in the culture medium. Our results show that, in the periphery, tolerance to oral Ag can be induced in both a Th1- or Th2-deficient environment. In the mucosa, however, the absence of Th1 and Th2 cytokines can markedly affect this response, perhaps by regulation of TGF-beta-secreting cells.
    The Journal of Immunology 06/1999; 162(9):5143-8. · 5.52 Impact Factor
  • Source
    G M Spiekermann, C Nagler-Anderson
    [Show abstract] [Hide abstract]
    ABSTRACT: The toxicity of the staphylococcal enterotoxins (SEs) has been linked to the activation of large numbers of T cells in the peripheral lymphoid tissues. Because the primary manifestations of foodborne enterotoxic poisoning are associated with the gastrointestinal tract, we have compared the responses of T cells in the gut-associated lymphoid tissue and in the periphery to intragastric (i.g.) and i.p. administration of SEB. Intraperitoneal SEB results in an early expansion of peripheral Vbeta8+ T cells and Th1 cytokine secretion followed by deletion at 7-10 days. We found that i.g. SEB rapidly (within 4 h) leads to the expansion and activation of Vbeta8+ T cells in the Peyer's patch and mesenteric lymph nodes. Analysis of cytokine mRNA in purified Vbeta8+ T cells by competitive RT-PCR showed that, 4 h after i.g. SEB, the induction of mRNA for IL-2 and IFN-gamma is about 10-fold greater in mucosal than in peripheral lymphoid tissue. Our results show that activated mucosal T cells expand and up-regulate cytokine mRNA in response to luminal exposure to SEB, suggesting a role for the gut-associated lymphoid tissue in the gastrointestinal manifestations of enterotoxic poisoning.
    The Journal of Immunology 01/1999; 161(11):5825-31. · 5.52 Impact Factor

Publication Stats

1k Citations
219.28 Total Impact Points

Institutions

  • 1998–2006
    • Harvard Medical School
      • Department of Pediatrics
      Boston, Massachusetts, United States
  • 1992–2006
    • Massachusetts General Hospital
      • • Mucosal Immunology Laboratory
      • • Center for the Study of Inflammatory Bowel Disease
      • • MassGeneral Hospital for Children
      Boston, MA, United States
  • 1999–2001
    • Harvard University
      Cambridge, Massachusetts, United States
  • 2000
    • Massachusetts Institute of Technology
      • Division of Comparative Medicine
      Cambridge, MA, United States