Proliferative responses of human intraepithelial lymphocytes to various T-cell stimuli

Ebert, Ellen C.

doi:10.1016/0016-5085(89)90379-x

Cited by 133 publications

(58 citation statements)

References 27 publications

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“…This may be due to the fact that gliadin-specific T cells are only generated in CD patients and that the normal immune system simply ignores this food Ag. Alternatively, the frequency of gliadin-specific T cells in the normal mucosa may be extremely low and/or they may have an intrinsically low proliferative capacity which hampers the possibility to clone them in vitro (34,35). By contrast, Tr1 cells specific for desmoglein 3, the autoantigen of pemphigus vulgaris, are found at high frequency in the peripheral blood of healthy donors and only in a minority of patients (36,37).…”

Section: Discussionmentioning

confidence: 99%

Gliadin-Specific Type 1 Regulatory T Cells from the Intestinal Mucosa of Treated Celiac Patients Inhibit Pathogenic T Cells

Gianfrani

Levings

Sartirana

et al. 2006

The Journal of Immunology

125

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Celiac disease (CD) results from a permanent intolerance to dietary gluten and is due to a massive T cell-mediated immune response to gliadin, the main component of gluten. In this disease, the regulation of immune responses to dietary gliadin is altered. Herein, we investigated whether IL-10 could modulate anti-gliadin immune responses and whether gliadin-specific type 1 regulatory T (Tr1) cells could be isolated from the intestinal mucosa of CD patients in remission. Short-term T cell lines were generated from jejunal biopsies, either freshly processed or cultured ex vivo with gliadin in the presence or absence of IL-10. Ex vivo stimulation of CD biopsies with gliadin in the presence of IL-10 resulted in suppression of Ag-specific proliferation and cytokine production, indicating that pathogenic T cells are susceptible to IL-10-mediated immune regulation. T cell clones generated from intestinal T cell lines were tested for gliadin specificity by cytokine production and proliferative responses. The majority of gliadin-specific T cell clones had a Th0 cytokine production profile with secretion of IL-2, IL-4, IFN-γ, and IL-10 and proliferated in response to gliadin. Tr1 cell clones were also isolated. These Tr1 cells were anergic, restricted by DQ2 (a CD-associated HLA), and produced IL-10 and IFN-γ, but little or no IL-2 or IL-4 upon activation with gliadin or polyclonal stimuli. Importantly, gliadin-specific Tr1 cell clones suppressed proliferation of pathogenic Th0 cells. In conclusion, dietary Ag-specific Tr1 cells are present in the human intestinal mucosa, and strategies to boost their numbers and/or function may offer new therapeutic opportunities to restore gut homeostasis.

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Section: Discussionmentioning

confidence: 99%

Gliadin-Specific Type 1 Regulatory T Cells from the Intestinal Mucosa of Treated Celiac Patients Inhibit Pathogenic T Cells

Gianfrani

Levings

Sartirana

et al. 2006

The Journal of Immunology

125

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“…Given that intraepithelial cells proliferate minimally in response to Ag and mitogen alike (55) and that we used exogenous Ags (MHC class II restricted) in our study, intraepithelial cells and CD8 ϩ cells are also unlikely to contribute to these responses.…”

Section: Discussionmentioning

confidence: 99%

Evidence for Naturally Acquired T Cell-Mediated Mucosal Immunity to Neisseria meningitidis

Davenport

Guthrie

Findlow

et al. 2003

The Journal of Immunology

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Naturally acquired protective immunity against Neisseria meningitidis is thought to partially explain the disparity between the high levels of carriage in the human nasopharynx and the rare incidence of disease. To investigate this immunity to Neisseria meningitidis at the mucosal level, in vitro cellular responses to outer membrane vesicle preparations derived from this pathogen were examined using mononuclear cells from the palatine tonsils of adults and children. Characterization of these responses was achieved by depletion of CD45RA+, CD45RO+, and CD19+ populations and outer membrane vesicles derived from isogenic mutants expressing different serosubtypes of the major outer membrane protein, porin A (PorA), no PorA and membrane preparations from a mutant with no LPS (LpxA−). The magnitude of cellular proliferative responses against the outer membrane vesicles were strongly associated with age and were largely T cell mediated, involving both CD45RO+ and CD45RA+ T cell phenotypes. Responses were not dependent on LPS but consisted of both PorA cross-specific and non-PorA-dependent responses. Cellular immunity against Neisseria meningitidis was found to be frequently associated with systemic IgG Abs but was not associated with serum bactericidal Abs. For the first time our results demonstrate an age-associated acquisition of mucosal T effector/memory cell responses to Neisseria meningitidis. This mucosal cellular immunity can be present in the absence of serum bactericidal Abs, a classical marker of protective immunity.

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“…IELs possess many unique functional properties not described with circulating human peripheral blood lymphocytes or murine IELs (14). For example, they respond minimally to triggering of the CD3/T cell receptor (TCR) pathway, indicating a limited response to antigen (6). Yet they proliferate briskly through the alternate CD2 pathway (6).…”

Section: Human Intestinal Intraepithelial Lymphocytes (Iels) Are Cd3mentioning

confidence: 99%

Human intestinal intraepithelial lymphocytes and epithelial cells coinduce interleukin-8 production through the CD2-CD58 interaction

Ebert¹,

Panja²,

Praveen³

2009

American Journal of Physiology-Gastrointestinal and Liver Physi

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Proliferative responses of human intraepithelial lymphocytes to various T-cell stimuli

Cited by 133 publications

References 27 publications

Gliadin-Specific Type 1 Regulatory T Cells from the Intestinal Mucosa of Treated Celiac Patients Inhibit Pathogenic T Cells

Gliadin-Specific Type 1 Regulatory T Cells from the Intestinal Mucosa of Treated Celiac Patients Inhibit Pathogenic T Cells

Evidence for Naturally Acquired T Cell-Mediated Mucosal Immunity to Neisseria meningitidis

Human intestinal intraepithelial lymphocytes and epithelial cells coinduce interleukin-8 production through the CD2-CD58 interaction

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