scholarly journals Behavior of  Visceral Leishmania donovani in an Experimentally Induced T Helper Cell 2 (Th2)-Associated Response Model

1997 ◽  
Vol 185 (5) ◽  
pp. 867-874 ◽  
Author(s):  
Henry W. Murray ◽  
June Hariprashad ◽  
Robert L. Coffman
Keyword(s):  
Leishmania Donovani ◽  
Systemic Infection ◽  
T Helper Cell ◽  
Interleukin 4 ◽  
Helper Cell ◽  
T Helper ◽  
Th2 Response ◽  
Ifn Γ ◽  
Type Response ◽  
Visceral Infection

Although implicated in the clinical expression of human visceral leishmaniasis, a disease-exacerbating T helper cell 2 (Th2)-associated immune response involving interleukin-4 (IL-4) and/ or IL-10 is not readily detectable in experimental visceral infection. To overcome this obstacle to analyzing visceral Leishmania donovani in this relevant immunopathogenetic environment, we sought a model in which a Th2 response induces noncuring infection. Four initial approaches were tested primarily in BALB/c mice which control intracellular L. donovani via an IL-12– and interferon-γ (IFN-γ)–dependent Th1 mechanism: (a) modifying the cytokine milieu when the parasite is first encountered (treatment with exogenous IL-4 or anti–IL-12), (b) providing sustained endogenous exposure to a Th2 cytokine (infection of IL-4 transgenic mice), (c) increasing the parasite challenge inoculum, and (d) injecting heat-killed L. major promastigotes (HKLMP) to induce a cross-reactive Th2 response to live L. donovani. Only the last approach generated a functional Th2-type response that induced disease exacerbation accompanied by inhibition of tissue granuloma assembly. In HKLMP-primed BALB/c mice, prophylaxis with anti–IL-4, anti–IL-10, or exogenous IL-12 (but not IFN-γ) readily restored resistance. In primed mice with established visceral infection, treatment with either IL-12 or IFN-γ also successfully induced antileishmanial activity. The results in this model (a) suggest that rather than acting alone, IL-4 and IL-10 may act in concert to prevent acquisition of resistance to L. donovani, (b) reemphasize the capacity of IL-12 to reverse early Th2-related effects, and (c) demonstrate that Th1 cytokines (IL-12, IFN-γ) have therapeutic action in an established systemic infection despite the presence of a disease-exacerbating Th2-type response.

scholarly journals The “one airway, one disease” concept in light of Th2 inflammation

2018 ◽  
Vol 52 (4) ◽  
pp. 1800437 ◽  
Author(s):  
Lisa Giovannini-Chami ◽  
Agnès Paquet ◽  
Céline Sanfiorenzo ◽  
Nicolas Pons ◽  
Julie Cazareth ◽  
...  
Keyword(s):  
Gene Expression ◽  
Allergic Rhinitis ◽  
Bronchial Epithelium ◽  
T Helper Cell ◽  
Polymorphonuclear Neutrophils ◽  
Helper Cell ◽  
T Helper ◽  
Th2 Response ◽  
Large Variability ◽  
Th2 Inflammation

In line with the pathophysiological continuum described between nose and bronchus in allergic respiratory diseases, we assessed whether nasal epithelium could mirror the Type 2 T-helper cell (Th2) status of bronchial epithelium.Nasal and bronchial cells were collected by brushing from healthy controls (C, n=13), patients with allergic rhinitis and asthma (AR, n=12), and patients with isolated allergic rhinitis (R, n=14). Cellular composition was assessed by flow cytometry, gene expression was analysed by RNA sequencing and Th2, Type 17 T-helper cell (Th17) and interferon (IFN) signatures were derived from the literature.Infiltration by polymorphonuclear neutrophils (PMN) in the nose excluded 30% of the initial cohort. All bronchial samples from the AR group were Th2-high. The gene expression profile of nasal samples from the AR group correctly predicted the paired bronchial sample Th2 status in 71% of cases. Nevertheless, nasal cells did not appear to be a reliable surrogate for the Th2 response, in particular due to a more robust influence of the IFN response in 14 out of 26 nasal samples. The Th2 scores in the nose and bronchi correlated with mast cell count (both p<0.001) and number of sensitisations (p=0.006 and 0.002), while the Th17 scores correlated with PMN count (p=0.006 and 0.003).The large variability in nasal cell composition and type of inflammation restricts its use as a surrogate for assessing bronchial Th2 inflammation in AR patients.

scholarly journals gp63 in Stable Cationic Liposomes Confers Sustained Vaccine Immunity to Susceptible BALB/c Mice Infected with Leishmania donovani

2008 ◽  
Vol 76 (3) ◽  
pp. 1003-1015 ◽  
Author(s):  
Swati Bhowmick ◽  
Rajesh Ravindran ◽  
Nahid Ali
Keyword(s):  
Visceral Leishmaniasis ◽  
Leishmania Donovani ◽  
Protective Efficacy ◽  
Cationic Liposomes ◽  
Interleukin 4 ◽  
Th2 Response ◽  
Parasitic Burden ◽  
Ifn Γ ◽  
Dose Dependent

ABSTRACT Visceral leishmaniasis is deadly if not treated, and development of a vaccine with long-term immunity remains a challenge. In this study, we showed that cationic distearoyl phosphatidylcholine (DSPC) liposomes, when used as vaccine adjuvant with the immunodominant 63-kDa glycoprotein (gp63) of Leishmania donovani promastigotes, induced significant protection against progressive visceral leishmaniasis in susceptible BALB/c mice. gp63 used without adjuvant elicited partial protection but in association with liposomes exhibited marked resistance in both the livers and spleens of the mice challenged 10 days after the last vaccination. The protective efficacy of liposomal gp63 vaccination was dose dependent, with 2.5 μg of protein showing optimal protection. The immunity conferred by this vaccine formulation was durable, as mice challenged 12 weeks after immunization were still protected, and the infection was controlled for at least 3 months postchallenge. Production of gamma interferon (IFN-γ) and interleukin-4 (IL-4) by splenic T cells, and of serum immunoglobulin G1 (IgG1) and IgG2a following immunization, suggested that a mixed Th1/Th2 response had been induced following immunization. However, control of disease progression and parasitic burden in mice vaccinated with gp63 in cationic DSPC liposomes was associated with enhancement of antigen-specific IFN-γ and downregulation of IL-4, demonstrating a Th1 bias. Long-term immunity elicited by this vaccine corresponded to, in addition to the presence of antigen-specific Th1, CD8+ T-cell responses. Our results demonstrated that stable cationic liposomes containing gp63 acted as a potent adjuvant for protein antigen to induce long-term protection against L. donovani that represents an alternative to DNA vaccination.

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 Interferon γ Stabilizes the T Helper Cell Type 1 Phenotype

2001 ◽  
Vol 194 (2) ◽  
pp. 165-172 ◽  
Author(s):  
Yongkang Zhang ◽  
Ron Apilado ◽  
John Coleman ◽  
Shlomo Ben-Sasson ◽  
Sharon Tsang ◽  
...  
Keyword(s):  
Critical Role ◽  
Interferon Γ ◽  
T Helper Cell ◽  
Helper Cell ◽  
Wild Type ◽  
T Helper ◽  
Helper Cell Type ◽  
Ifn Γ ◽  
Th 1

T helper cell (Th)1-primed CD4 T cells from wild-type donors make little interleukin (IL)-4 when restimulated under Th2 conditions. However, such restimulation of Th1-primed cells from interferon (IFN)-γ2/− or IFN-γ receptor (IFN-γR)−/− mice resulted in substantial production of IL-4 and other Th2 cytokines. Adding IFN-γ to the priming culture markedly diminished the capacity of Th1-primed IFN-γ2/− cells to express IL-4. Even IFN-γ–producing cells from IFN-γR−/− mice could acquire IL-4–producing capacity. Thus, IFN-γ is not required for the development of IFN-γ–producing capacity, but it plays a critical role in suppressing the IL-4–producing potential of Th1 cells.

scholarly journals Pathogenicity and Immune Response Measured in Mice following Intranasal Challenge with Enterotoxigenic Escherichia coli Strains H10407 and B7A

2003 ◽  
Vol 71 (1) ◽  
pp. 13-21 ◽  
Author(s):  
Wyatt Byrd ◽  
Steven R. Mog ◽  
Frederick J. Cassels
Keyword(s):  
Escherichia Coli ◽  
T Helper Cell ◽  
Enterotoxigenic Escherichia Coli ◽  
Helper Cell ◽  
T Helper ◽  
Th2 Response ◽  
Igm Antibody ◽  
Serum Igg ◽  
Antibody Titers ◽  
Low Serum

ABSTRACT The pathogenicity and immunogenicity induced in BALB/c mice by intranasal (i.n.) inoculation of enterotoxigenic Escherichia coli (ETEC) strains H10407 (O78:H11:CFA/I:LT+:ST+) and B7A (O148:H28:CS6:LT+:ST+) (two ETEC strains previously used in human challenge trials) were studied. The i.n. inoculation of BALB/c mice with large doses of ETEC strains H10407 and B7A caused illness and death. The H10407 strain was found to be consistently more virulent than the B7A strain. Following i.n. challenge with nonlethal doses of H10407 and B7A, the bacteria were cleared from the lungs of the mice at a steady rate over a 2-week period. Macrophages and neutrophils were observed in the alveoli and bronchioles, and lymphocytes were observed in the septa, around vessels, and in the pleura of the lungs in mice challenged with H10407 and B7A. In mice i.n. challenged with H10407, serum immunoglobulin G (IgG) and IgM antibodies were measured at high titers to the CFA/I and O78 lipopolysaccharide (LPS) antigens. In mice i.n. challenged with B7A, low serum IgG antibody titers were detected against CS6, and low serum IgG and IgM antibody titers were detected against O148 LPS. The serum IgG and IgM antibody titers against the heat-labile enterotoxin were equivalent in the H10407- and B7A-challenged mice. The CFA/I and O78 LPS antigens gave mixed T-helper cell 1-T-helper cell 2 (Th1-Th2) responses in which the Th2 response was greater than the Th1 response (i.e., stimulated primarily an antibody response). These studies indicate that the i.n. challenge of BALB/c mice with ETEC strains may provide a useful animal model to better understand the immunogenicity and pathogenicity of ETEC and its virulence determinants. This model may also be useful in providing selection criteria for vaccine candidates for use in primate and human trials.

scholarly journals Mercuric chloride, a chemical responsible for T helper cell (Th)2-mediated autoimmunity in brown Norway rats, directly triggers T cells to produce interleukin-4.

1995 ◽  
Vol 96 (3) ◽  
pp. 1484-1489 ◽  
Author(s):  
P Prigent ◽  
A Saoudi ◽  
C Pannetier ◽  
P Graber ◽  
J Y Bonnefoy ◽  
...  
Keyword(s):  
T Cells ◽  
Mercuric Chloride ◽  
T Helper Cell ◽  
Interleukin 4 ◽  
Helper Cell ◽  
Brown Norway ◽  
T Helper ◽  
Norway Rats

scholarly journals Inhibition of IFN-γ transcription by site-specific methylation during T helper cell development

2006 ◽  
Vol 25 (11) ◽  
pp. 2443-2452 ◽  
Author(s):  
Brendan Jones ◽  
Jianzhu Chen
Keyword(s):  
Cell Development ◽  
T Helper Cell ◽  
Helper Cell ◽  
T Helper ◽  
Site Specific ◽  
Ifn Γ

scholarly journals Stroke-induced Immunodeficiency Promotes Spontaneous Bacterial Infections and Is Mediated by Sympathetic Activation Reversal by Poststroke T Helper Cell Type 1–like Immunostimulation

2003 ◽  
Vol 198 (5) ◽  
pp. 725-736 ◽  
Author(s):  
Konstantin Prass ◽  
Christian Meisel ◽  
Conny Höflich ◽  
Johann Braun ◽  
Elke Halle ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Focal Cerebral Ischemia ◽  
Lymphocyte Activation ◽  
T Helper Cell ◽  
Helper Cell ◽  
T Helper ◽  
Th2 Cytokine ◽  
Key Factor ◽  
Helper Cell Type ◽  
Ifn Γ

Infections are a leading cause of death in stroke patients. In a mouse model of focal cerebral ischemia, we tested the hypothesis that a stroke-induced immunodeficiency increases the susceptibility to bacterial infections. 3 d after ischemia, all animals developed spontaneous septicemia and pneumonia. Stroke induced an extensive apoptotic loss of lymphocytes and a shift from T helper cell (Th)1 to Th2 cytokine production. Adoptive transfer of T and natural killer cells from wild-type mice, but not from interferon (IFN)-γ–deficient mice, or administration of IFN-γ at day 1 after stroke greatly decreased the bacterial burden. Importantly, the defective IFN-γ response and the occurrence of bacterial infections were prevented by blocking the sympathetic nervous system but not the hypothalamo-pituitary-adrenal axis. Furthermore, administration of the β-adrenoreceptor blocker propranolol drastically reduced mortality after stroke. These data suggest that a catecholamine-mediated defect in early lymphocyte activation is the key factor in the impaired antibacterial immune response after stroke.

Comprehensive Intestinal T Helper Cell Profiling Reveals Specific Accumulation of IFN-γ+IL-17+Coproducing CD4+ T Cells in Active Inflammatory Bowel Disease

2014 ◽  
Vol 20 (12) ◽  
pp. 2321-2329 ◽  
Author(s):  
Anna-Maria Globig ◽  
Nadine Hennecke ◽  
Bianca Martin ◽  
Maximilian Seidl ◽  
Günther Ruf ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
T Cells ◽  
Bowel Disease ◽  
Cd4 T Cells ◽  
T Helper Cell ◽  
Helper Cell ◽  
T Helper ◽  
Specific Accumulation ◽  
Inflammatory Bowel ◽  
Ifn Γ

Melatonin-induced T-helper cell hematopoietic cytokines resembling both interleukin-4 and dynorphin

1996 ◽  
Vol 21 (3) ◽  
pp. 131-139 ◽  
Author(s):  
Georges J. M. Maestroni ◽  
Elisabeth Hertens ◽  
Paola Galli ◽  
Ario Conti ◽  
Ennio Pedrinis
Keyword(s):  
T Helper Cell ◽  
Interleukin 4 ◽  
Helper Cell ◽  
T Helper
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