γδ T‐cell clones from intestinal intraepithelial lymphocytes inhibit development of CTL responses <i>ex vivo</i>

Kapp, Judith A.; Kapp, Linda M.; McKenna, Kyle C.; Lake, Jeffrey P.

doi:10.1111/j.0019-2805.2003.01793.x

Cited by 50 publications

(43 citation statements)

References 49 publications

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“…29) It has been reported that TCRgd-T cells produce the regulatory cytokine transforming growth factor-b1 (TGF-b1) in vitro and induce oral tolerance in vivo, 30) suggesting that the TCRgd-T cells among the IELs produce the regulatory cytokines (TGF-b1 and/or IL-10) upon stimulation and function as regulatory T cells which inhibit antigen-specific T cells. 31) In conclusion, the decrease in the number of gd-IELs caused by anti-TCRgd antibody treatment increased oral sensitization of wild-type (ϩ/ϩ) mice. The increase in the number of gd-IELs seems to be involved in the production of oral tolerance.…”

Section: Discussionmentioning

confidence: 85%

The Hyperresponsiveness of W/Wv Mice to Oral Sensitization Is Associated with a Decrease in TCR.GAMMA..DELTA.-T Cells

Okunuki

Teshima

Sato

et al. 2005

Biological & Pharmaceutical Bulletin

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The number of patients with food allergies has been increasing for various reasons (e.g., changes in diet, increased stress, etc.), but the mechanisms of the development and regulation of food allergy have not yet been fully elucidated. Thus, oral sensitization models in animals are important for better understanding the induction and regulation mechanisms of food allergy. [1][2][3] When the allergenicity of dietary proteins is evaluated in animal, it is desirable to perform the sensitization orally, preferably without using adjuvants. However, since orally administered food antigens induce tolerance by various mechanisms, [4][5][6] it is important to optimize the dosage of the allergen and the duration of immunization in order to achieve oral sensitization without inducing tolerance.In previous studies, we compared animal food allergy models using various strains of mice and rat, 7) and found that significant antigen-specific antibody production was successfully induced without any adjuvant by orally administering OVA for 9 weeks in B10A mice and BALB/c mice. More recently, W/W v mice have been proven to be a good responder to food allergens, because their antigen-specific antibody titer was much higher than in the other murine strains used. 8)It is important to clarify the cause of the high susceptibility of the W/W v mice to oral sensitization in order to elucidate the mechanism of development of food allergy.W/W v mice have mutations in the c-kit gene and exhibit defects or a deficiency of mast cells, red blood cells, and interstitial cells of Cajal, which ordinarily express c-kit protein.9,10) The c-kit protein is a member of the type III receptor tyrosine kinase family, and its dimer is a ligand for the stem cell factor (SCF).11) We have reported low susceptibility of the congenic wild-type (ϩ/ϩ) mice to oral sensitization. The lack of high sensitivity in c-kit-positive wild-type (ϩ/ϩ) mice suggested that the susceptibility of W/W v mice to oral sensitization is related to the mutations in the c-kit gene.12)The population of gd-IELs is much smaller in W/W v mice than in wild-type mice.12) Moreover, it has been demonstrated that the ratio of the gd-IELs to total T cells in mouse intestinal mucosa is much higher than in other peripheral lymphoid tissues, 13) and that gd-IELs have been found to develop thymus independently in cryptopatches (CPs), which are located in the lamina propria. CPs are the small clusters of immature lymphocytes (c-kitϩ, IL-7Rϩ, Thy-1ϩ, LFA-1ϩ).14,15) Thus, gd-IELs are thought to play an important role in immune responses in the mucosa, although their function in oral sensitization is not fully understood. 16)The objective of this study was to identify the cause of the high susceptibility of W/W v mice to oral sensitization, and we performed two experiments to achieve this objective. In the first experiment, congenic wild-type (ϩ/ϩ) mice were treated with the anti-TCRgd antibody before oral sensitization to OVA. In the second experiment, bone marrow cell-reconstituted W/W v mice with ...

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Section: Discussionmentioning

confidence: 85%

The Hyperresponsiveness of W/Wv Mice to Oral Sensitization Is Associated with a Decrease in TCR.GAMMA..DELTA.-T Cells

Okunuki

Teshima

Sato

et al. 2005

Biological & Pharmaceutical Bulletin

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“…The induction of ACAID involves a complex series of events and the participation of at least four organs (eye, thymus, spleen, and sympathetic nervous system) and at least six different cell populations (ocular APCs (3), B cells (7,8), ␥␦ T cells (14,45,50), NKT cells (32,51), CD4 ϩ T cells (5,6), and CD8 ϩ T cells (36)). After capturing Ag in the AC, F4/80 ϩ ocular APCs migrate to the thymus (33) and spleen (52).…”

Section: Discussionmentioning

confidence: 99%

“…We considered the obvious explanation that ␥␦ T cells acted as efferent Treg cells that inhibited the expression of DTH, as ␥␦ T cells are known to secrete immunosuppressive and anti-inflammatory molecules (45). Moreover, some ␥␦ T cell populations express the CD8 molecule, which is also found on ACAID efferent Tregs (11).…”

Section: Discussionmentioning

confidence: 99%

“…Other reports have suggested that the immunosuppressive function of ␥␦ T cells is mediated mainly by cytokines (42,45). Because ACAID is a Th2-like phenomenon with an immunosuppressive consequence, we hypothesized that ␥␦ T cells need to secrete Th2 cytokines (such as IL-10 and IL-4) for the generation of efferent Tregs and down-regulation of DTH.…”

Section: ␥␦ T Cells Must Produce Il-10 To Induce Acaidmentioning

confidence: 97%

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γδ T Cells Promote Anterior Chamber-Associated Immune Deviation and Immune Privilege through Their Production of IL-10

Ashour¹,

Niederkorn

2006

The Journal of Immunology

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Anterior chamber-associated immune deviation (ACAID) is a form of peripheral tolerance that is induced by introducing Ags into the anterior chamber (AC) of the eye, and is maintained by Ag-specific regulatory T cells (Tregs). ACAID regulates harmful immune responses that can lead to irreparable injury to innocent bystander cells that are incapable of regeneration. This form of immune privilege in the eye is mediated through Tregs and is a product of complex cellular interactions. These involve F4/80+ ocular APCs, B cells, NKT cells, CD4+CD25+ Tregs, and CD8+ Tregs. γδ T cells are crucial for the generation of ACAID and for corneal allograft survival. However, the functions of γδ T cells in ACAID are unknown. Several hypotheses were proposed for determining the functions of γδ T cells in ACAID. The results indicate that γδ T cells do not cause direct suppression of delayed-type hypersensitivity nor do they act as tolerogenic APCs. In contrast, γδ T cells were shown to secrete IL-10 and facilitate the generation of ACAID Tregs. Moreover, the contribution of γδ T cells ACAID generation could be replaced by adding exogenous recombinant mouse IL-10 to ACAID spleen cell cultures lacking γδ T cells.

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“…TCRδ-deficient mice, which lack TCRγδ + T cells, demonstrate exaggerated intestinal mucosal damage in response to parasitic infections (25). In addition, murine small intestinal TCRγδ + IELs have been shown to express TGF-β mRNA, secrete IL-10, and inhibit cytotoxic T cell responses in vitro (26).…”

Section: Introductionmentioning

confidence: 99%

Small intestinal CD8+TCRγδ+NKG2A+ intraepithelial lymphocytes have attributes of regulatory cells in patients with celiac disease

Bhagat¹,

Naiyer²,

Shah³

et al. 2008

J. Clin. Invest.

173

146

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γδ T‐cell clones from intestinal intraepithelial lymphocytes inhibit development of CTL responses ex vivo

Cited by 50 publications

References 49 publications

The Hyperresponsiveness of W/Wv Mice to Oral Sensitization Is Associated with a Decrease in TCR.GAMMA..DELTA.-T Cells

The Hyperresponsiveness of W/Wv Mice to Oral Sensitization Is Associated with a Decrease in TCR.GAMMA..DELTA.-T Cells

γδ T Cells Promote Anterior Chamber-Associated Immune Deviation and Immune Privilege through Their Production of IL-10

Small intestinal CD8+TCRγδ+NKG2A+ intraepithelial lymphocytes have attributes of regulatory cells in patients with celiac disease

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