scholarly journals Crucial Role of the Interleukin 1 Receptor Family Member T1/St2 in T Helper Cell Type 2–Mediated Lung Mucosal Immune Responses

1999 ◽  
Vol 190 (7) ◽  
pp. 895-902 ◽  
Author(s):  
Anthony J. Coyle ◽  
Clare Lloyd ◽  
Jane Tian ◽  
Trang Nguyen ◽  
Christina Erikkson ◽  
...  
Keyword(s):  
Immune Responses ◽  
T Helper Cell ◽  
Helper Cell ◽  
Eosinophil Infiltration ◽  
Cell Type ◽  
T Helper ◽  
Helper Cell Type ◽  
Mucosal Immune Responses

T1/ST2 is an orphan receptor of unknown function that is expressed on the surface of murine T helper cell type 2 (Th2), but not Th1 effector cells. In vitro blockade of T1/ST2 signaling with an immunoglobulin (Ig) fusion protein suppresses both differentiation to and activation of Th2, but not Th1 effector populations. In a nascent Th2-dominated response, anti-T1/ST2 monoclonal antibody (mAb) inhibited eosinophil infiltration, interleukin 5 secretion, and IgE production. To determine if these effects were mediated by a direct effect on Th2 cells, we next used a murine adoptive transfer model of Th1- and Th2-mediated lung mucosal immune responses. Administration of either T1/ST2 mAb or T1/ST2-Ig abrogated Th2 cytokine production in vivo and the induction of an eosinophilic inflammatory response, but failed to modify Th1-mediated inflammation. Taken together, our data demonstrate an important role of T1/ST2 in Th2-mediated inflammatory responses and suggest that T1/ST2 may prove to be a novel target for the selective suppression of Th2 immune responses.

scholarly journals T1/St2-Deficient Mice Demonstrate the Importance of T1/St2 in Developing Primary T Helper Cell Type 2 Responses

2000 ◽  
Vol 191 (6) ◽  
pp. 1069-1076 ◽  
Author(s):  
Michael J. Townsend ◽  
Padraic G. Fallon ◽  
David J. Matthews ◽  
Helen E. Jolin ◽  
Andrew N.J. McKenzie
Keyword(s):  
T Helper Cell ◽  
Helper Cell ◽  
Eosinophil Infiltration ◽  
Wild Type ◽  
Cell Type ◽  
T Helper ◽  
Helper Cell Type ◽  
Pulmonary Granuloma ◽  
Deficient Mice

We have generated mice with a deficiency in T1/ST2 expression to clarify the roles of T1/ST2 in T helper cell type 2 (Th2) responses. Using immunological challenges normally characterized by a Th2-like response, we have compared the responses of T1/ST2-deficient mice with those generated by wild-type mice. Using a primary pulmonary granuloma model, induced with Schistosoma mansoni eggs, we demonstrate that granuloma formation, characterized by eosinophil infiltration, is abrogated in T1/ST2-deficient mice. Furthermore, we clearly demonstrate that in the absence of T1/ST2 expression, the levels of Th2 cytokine production are severely impaired after immunization. Thus, in a secondary pulmonary granuloma model, draining lymph node cells from the T1/ST2-deficient animals produced significantly reduced levels of IL-4 and IL-5, despite developing granulomas of a magnitude similar to those of wild-type mice and comparable antigen-specific immunoglobulin isotype production. These data clearly demonstrate that T1/ST2 expression plays a role in the development of Th2-like cytokine responses and indicate that effector functions are inhibited in its absence.

scholarly journals T Helper Cell Type 2 Responsiveness Predicts Future Susceptibility to Gastrointestinal Nematodes in Humans

2004 ◽  
Vol 190 (10) ◽  
pp. 1804-1811 ◽  
Author(s):  
Joseph A. Jackson ◽  
Joseph D. Turner ◽  
Lawrence Rentoul ◽  
Helen Faulkner ◽  
Jerzy M. Behnke ◽  
...  
Keyword(s):  
Gastrointestinal Nematodes ◽  
T Helper Cell ◽  
Helper Cell ◽  
Cell Type ◽  
T Helper ◽  
Helper Cell Type

Fetal Phagocytes Take up Allergens to Initiate T-Helper Cell Type 2 Immunity and Facilitate Allergic Airway Responses

2016 ◽  
Vol 194 (8) ◽  
pp. 934-947 ◽  
Author(s):  
Jeng-Chang Chen ◽  
Cheng-Chi Chan ◽  
Chia-Jen Wu ◽  
Liang-Shiou Ou ◽  
Hsiu-Yueh Yu ◽  
...  
Keyword(s):  
T Helper Cell ◽  
Helper Cell ◽  
Cell Type ◽  
T Helper ◽  
Type 2 Immunity ◽  
Helper Cell Type ◽  
Airway Responses

scholarly journals Lipopolysaccharide-enhanced, Toll-like Receptor 4–dependent T Helper Cell Type 2 Responses to Inhaled Antigen

2002 ◽  
Vol 196 (12) ◽  
pp. 1645-1651 ◽  
Author(s):  
Stephanie C. Eisenbarth ◽  
Damani A. Piggott ◽  
James W. Huleatt ◽  
Irene Visintin ◽  
Christina A. Herrick ◽  
...  
Keyword(s):  
Allergic Sensitization ◽  
T Helper Cell ◽  
Helper Cell ◽  
Asthma Prevalence ◽  
Cell Type ◽  
T Helper ◽  
Th2 Responses ◽  
Helper Cell Type ◽  
Lps Signaling

Allergic asthma is an inflammatory lung disease initiated and directed by T helper cells type 2 (Th2). The mechanism involved in generation of Th2 responses to inert inhaled antigens, however, is unknown. Epidemiological evidence suggests that exposure to lipopolysaccharide (LPS) or other microbial products can influence the development and severity of asthma. However, the mechanism by which LPS influences asthma pathogenesis remains undefined. Although it is known that signaling through Toll-like receptors (TLR) is required for adaptive T helper cell type 1 (Th1) responses, it is unclear if TLRs are needed for Th2 priming. Here, we report that low level inhaled LPS signaling through TLR4 is necessary to induce Th2 responses to inhaled antigens in a mouse model of allergic sensitization. The mechanism by which LPS signaling results in Th2 sensitization involves the activation of antigen-containing dendritic cells. In contrast to low levels, inhalation of high levels of LPS with antigen results in Th1 responses. These studies suggest that the level of LPS exposure can determine the type of inflammatory response generated and provide a potential mechanistic explanation of epidemiological data on endotoxin exposure and asthma prevalence.

scholarly journals Oxazolone Colitis: A Murine Model of  T Helper Cell Type 2 Colitis Treatable with Antibodies to Interleukin 4

1998 ◽  
Vol 188 (10) ◽  
pp. 1929-1939 ◽  
Author(s):  
Monica Boirivant ◽  
Ivan J. Fuss ◽  
Alan Chu ◽  
Warren Strober
Keyword(s):  
T Cells ◽  
Transforming Growth Factor ◽  
Fold Increase ◽  
T Helper Cell ◽  
Interleukin 4 ◽  
Helper Cell ◽  
Cell Type ◽  
T Helper ◽  
Helper Cell Type

In this study we describe oxazolone colitis, a new form of experimental colitis. This model is induced in SJL/J mice by the rectal instillation of the haptenating agent, oxazolone, and is characterized by a rapidly developing colitis confined to the distal half of the colon; it consists of a mixed neutrophil/lymphocyte infiltration limited to the superficial layer of the mucosa which is associated with ulceration. Oxazolone colitis is a T helper cell type 2 (Th2)-mediated process since stimulated T cells from lesional tissue produce markedly increased amounts of interleukin (IL)-4 and IL-5; in addition, anti–IL-4 administration leads to a striking amelioration of disease, whereas anti–IL-12 administration either has no effect or exacerbates disease. Finally, this proinflammatory Th2 cytokine response is counterbalanced by a massive transforming growth factor-β (TGF-β) response which limits both the extent and duration of disease: lesional (distal) T cells manifest a 20–30-fold increase in TGF-β production, whereas nonlesional (proximal) T cells manifest an even greater 40–50-fold increase. In addition, anti–TGF-β administration leads to more severe inflammation which now involves the entire colon. The histologic features and distribution of oxazolone colitis have characteristics that resemble ulcerative colitis (UC) and thus sharply distinguish this model from most other models, which usually resemble Crohn's disease. This feature of oxazolone colitis as well as its cytokine profile have important implications to the pathogenesis and treatment of UC.

scholarly journals c-maf Promotes T Helper Cell Type 2 (Th2) and Attenuates Th1 Differentiation by Both Interleukin 4–dependent and –independent Mechanisms

1998 ◽  
Vol 188 (10) ◽  
pp. 1859-1866 ◽  
Author(s):  
I-Cheng Ho ◽  
David Lo ◽  
Laurie H. Glimcher
Keyword(s):  
Transgenic Mice ◽  
Ectopic Expression ◽  
T Helper Cell ◽  
Helper Cell ◽  
Th2 Cytokines ◽  
Cell Type ◽  
T Helper ◽  
Helper Cell Type

The c-maf protooncogene is a T helper cell type 2 (Th2)-specific transcription factor that activates the interleukin (IL)-4 promoter in vitro. Although it has been postulated that c-maf directs the Th2-specific expression of the IL-4 gene in vivo, direct evidence that c-maf functions during the differentiation of normal, primary T cells is lacking. We now demonstrate that overexpression of c-maf in vivo skews the Th immune response along a Th2 pathway, as evidenced by increased production of Th2 cytokines and the IL-4–dependent immunoglobulins, IgG1 and IgE. The overproduction of IgGl and IgE in the CD4 promoter/c-maf transgenic mice was IL-4 dependent since this was not observed in c-maf transgenic mice bred onto an IL-4–deficient background. Ectopic expression of c-maf in mature Th1 cells did not confer on them the ability to produce IL-4, but did decrease the production of IFN-γ. The attenuation of Th1 differentiation by c-maf overexpression occurred by a mechanism that was independent of IL-4 and other Th2 cytokines, and could be overcome by IL-12. These studies demonstrate that c-maf promotes Th2 differentiation by IL-4–dependent mechanisms and attenuates Th1 differentiation by Th2 cytokine-independent mechanisms.

Sign in / Sign up

Export Citation Format

Share Document