Costimulation through B7-2 (CD86) Is Required for the Induction of a Lung Mucosal T Helper Cell 2 (TH2) Immune Response and Altered Airway Responsiveness

Tsuyuki, Shogo; Tsuyuki, Junko; Einsle, Karin; Köpf, Manfred; Coyle, Anthony J.

doi:10.1084/jem.185.9.1671

Cited by 232 publications

(165 citation statements)

References 49 publications

Supporting

Mentioning

154

Contrasting

Order By: Relevance

“…Thus, APC in splenocyte culture appear to be capable of providing additional stimuli such as cytokines or costimulatory molecules that aid development of IL-4-producing ␥␦ T cells. This is consistent with the general notion that the generation of a Th2 response is more dependent on costimulation than is generation of a Th1 response (50,51).…”

Section: Discussionsupporting

confidence: 91%

Dominance of IL-12 Over IL-4 in γδ T Cell Differentiation Leads to Default Production of IFN-γ: Failure to Down-Regulate IL-12 Receptor β2-Chain Expression

Yin

Zhang

Welte³

et al. 2000

The Journal of Immunology

View full text Add to dashboard Cite

γδ T cells secrete Th1- and Th2-like cytokines that help mediate innate and acquired immunity. We have addressed the mechanism whereby murine γδ T cells acquire the capacity to differentially produce such cytokines. Splenic γδ T cells could be polarized into IFN-γ- or IL-4-secreting cells in vitro; however, in contrast to CD4+ αβ T cells, γδ T cells predominantly produced IFN-γ, even in the presence of IL-4, a finding independent of genetic background. Like CD4+ Th1 cells, IFN-γ-producing cells expressed the IL-12 receptor β2-chain after activation in the presence of IL-12; however, unlike Th2 cells, IL-4-primed γδ T cells also expressed this receptor, even in the absence of IFN-γ and despite the presence of the transcription factor GATA-3. IL-12 also induced IL-4-primed γδ T cells to proliferate and to translocate Stat3/Stat4, indicating signaling through the IL-12 receptor. These molecular events can account for the predominant production of IFN-γ by γδ T cells in the presence of IL-12, despite the availability of IL-4. Early and predominant production of IFN-γ by γδ T cells likely is critical for the roles that these cells play in protection against intracellular pathogens and in tumor immunity.

show abstract

Section: Discussionsupporting

confidence: 91%

Dominance of IL-12 Over IL-4 in γδ T Cell Differentiation Leads to Default Production of IFN-γ: Failure to Down-Regulate IL-12 Receptor β2-Chain Expression

Yin

Zhang

Welte³

et al. 2000

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…This does not support delivering small volumes as a means to localize distribution to the respiratory tract, as has been claimed (2). Furthermore, our results are in disagreement with those of Tsuyuki et al (23), who did not detect any Evans blue dye in the esophagus or stomach after intranasal instillation of 50 l. Possibly these measurements were made immediately after instillation, when distribution to the GI tract is still relatively small.…”

Section: Discussioncontrasting

confidence: 57%

Distribution of intranasal instillations in mice: effects of volume, time, body position, and anesthesia

Southam

Dolovich

O’Byrne

et al. 2002

American Journal of Physiology-Lung Cellular and Molecular Phys

287

243

View full text Add to dashboard Cite

Intranasal instillation techniques are used to deliver various substances to the upper and lower respiratory tract (URT and LRT) in mice. Here, we quantify the relative distribution achieved with intranasal delivery of a nonabsorbable tracer, 99m Tc-labeled sulfidecolloid. Relative distribution was determined by killing mice after instillation and quantifying the radioactivity in dissected tissues using gamma scintigraphy. A significant effect of delivery volume on relative distribution was observed when animals were killed 5 min after instillation delivered under gas anesthesia. With a delivery volume of 5 l, no radiation was detected in the LRT; this increased to a maximum of 55.7 Ϯ 2.5% distribution to the LRT when 50 l were delivered. The majority of radiation not detected in the LRT was found in the URT. Over the course of the following 1 h, radiation in the LRT remained constant, while that in the URT decreased and appeared in the gastrointestinal tract. Instillation of 25 l into anesthetized mice resulted in 30.1 Ϯ 6.9% distribution to the LRT, while only 5.3 Ϯ 1.5% (P Ͻ 0.05) of the same volume was detected in the LRT of awake mice. Varying the body position of mice did not affect relative distribution. When using intranasal instillation, the relative distribution between the URT and LRT and the gastrointestinal tract is heavily influenced by delivery volume and level of anesthesia. gamma scintigraphy; topical treatment; upper respiratory tract; lower respiratory tract THE ADMINISTRATION OF SUBSTANCES to mice by the intranasal route is an effective, noninvasive technique employed for the delivery of allergens (3, 4, 26), drugs or gene therapy (4, 20), immunotherapy (1, 7, 11), and pathogens (12,16,18) to the upper and lower respiratory tracts (URT and LRT). In published studies, volumes of substances intranasally instilled into mice range from 5 l (22) to 100 l (3), with little justification for the chosen volumes. Intranasal delivery is often carried out after intraperitoneal (9, 19) or inhalation (5, 14, 15) anesthesia but has also been performed with fully awake mice (1,6,17). The position of the mouse during intranasal delivery has also varied between studies, with horizontal (13) and head-down supine (12) positions having been used. The specific delivery protocols used in these studies are thought to influence the relative distribution of the delivered substance to the URT, LRT, and gut. However, to our knowledge, very little published information is available describing the distribution of intranasally delivered substances or how the distribution can be influenced by delivery techniques.Preliminary studies by Tsuyuki et al. (23) have shown that 75% of a 50-l dose of intranasally administered Evans blue dye is deposited in the airways, with no dye detectable in the esophagus or stomach. Eyles et al. (7) reported that 48% of a 50-l dose of intranasally instilled 7-m-diameter 46 Sc-labeled styrene-divinyl benzene microspheres was evident in the lungs 15 min after challenge, while Takafuji et al. (21) ...

show abstract

“…The type of Th cell responses to Ags encountered on the mucosal surfaces of the respiratory tract may be influenced by regional environmental factors, such as the nature of regional innate immunity (59) and the expression of costimulatory molecules (60,61).…”

Section: Discussionmentioning

confidence: 99%

T Cell Vaccination in Mice with Invasive Pulmonary Aspergillosis

Cenci

Mencacci

Bacci

et al. 2000

The Journal of Immunology

204

166

View full text Add to dashboard Cite

Aspergillus fumigatus, an opportunistic fungal pathogen, is responsible for multiple airway diseases of an allergic and a nonallergic nature. In a murine model of invasive pulmonary aspergillosis, resistance is associated with a decreased lung inflammatory pathology and the occurrence of an IL-12-dependent Th1-type reactivity that are both impaired by IL-4. In the present study we assess the ability of Aspergillus crude culture filtrate Ags and the recombinant allergen Asp f 2 to induce protective antifungal responses in mice with invasive pulmonary aspergillosis. Similar to what occurred upon nasal exposure to viable A. fumigatus conidia, treatment of immunocompetent mice with Aspergillus crude culture filtrate Ags resulted in the development of local and peripheral protective Th1 memory responses, mediated by Ag-specific CD4+ T cells producing IFN-γ and IL-2 capable of conferring protection upon adoptive transfer to naive recipients. Protective Th1 responses could not be observed in mice deficient of IFN-γ or IL-12 and did not occur in response to Asp f 2, which, on the contrary, elicited high level production of inhibitory IL-4. The results show that Ags of Aspergillus exist with the ability to induce both Th1- and Th2-type reactivity during infection, a finding that suggests a possible mechanism through which potentially protective immune responses are inhibited in mice with the infection. However, the occurrence of Th1-mediated resistance upon vaccination with Aspergillus crude culture filtrate Ags, suggests the existence of fungal Ags useful as a candidate vaccine against invasive pulmonary aspergillosis.

show abstract

Costimulation through B7-2 (CD86) Is Required for the Induction of a Lung Mucosal T Helper Cell 2 (TH2) Immune Response and Altered Airway Responsiveness

Cited by 232 publications

References 49 publications

Dominance of IL-12 Over IL-4 in γδ T Cell Differentiation Leads to Default Production of IFN-γ: Failure to Down-Regulate IL-12 Receptor β2-Chain Expression

Dominance of IL-12 Over IL-4 in γδ T Cell Differentiation Leads to Default Production of IFN-γ: Failure to Down-Regulate IL-12 Receptor β2-Chain Expression

Distribution of intranasal instillations in mice: effects of volume, time, body position, and anesthesia

T Cell Vaccination in Mice with Invasive Pulmonary Aspergillosis

Contact Info

Product

Resources

About