The role of CD40 in peripheral T cell tolerance and immunity

Diehl, Linda; Boer, Annemieke Th. den; Voort, Ellen I. H. van der; Melief, Cornelis J.M.; Offringa, Rienk; Toes, René E. M.

doi:10.1007/s001090000126

Cited by 68 publications

(50 citation statements)

References 66 publications

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“…In accord, we tested for LIGHT correlation with T cell activation as marked by up-regulation of surface markers OX40 (CD134) and CD40L (CD154) (39,40). PBL were surface stained for CD4/8, LIGHT, and OX40 or CD40L following P/I activation, indicating higher LIGHT expression levels in CD4 ϩ T cells expressing OX40 (Fig.…”

Section: Characterization Of Light-expressing T Cell Subsets In Peripmentioning

confidence: 99%

LIGHT Expression by Mucosal T Cells May Regulate IFN-γ Expression in the Intestine

Cohavy

Zhou

Granger

et al. 2004

The Journal of Immunology

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The TNF superfamily of cytokines play an important role in T cell activation and inflammation. Sustained expression of lymphotoxin-like inducible protein that competes with glycoprotein D for binding herpesvirus entry mediator on T cells (LIGHT) (TNFSF14) causes a pathological intestinal inflammation when constitutively expressed by mouse T cells. In this study, we characterized LIGHT expression on activated human T cell subsets in vitro and demonstrated a direct proinflammatory effect on regulation of IFN-γ. LIGHT was induced in memory CD45RO CD4+ T cells and by IFN-γ-producing CD4+ T cells. Kinetic analysis indicated rapid induction of LIGHT by human lamina propria T cells, reaching maximal levels by 2–6 h, whereas peripheral blood or lymph node-derived T cells required 24 h. Further analysis of intestinal specimens from a 41 patient cohort by flow cytometry indicated membrane LIGHT induction to higher peak levels in lamina propria T cells from the small bowel or rectum but not colon, when compared with lymph node or peripheral blood. Independent stimulation of the LIGHT receptor, herpesvirus entry mediator, induced IFN-γ production in lamina propria T cells, while blocking LIGHT inhibited CD2-dependent induction of IFN-γ synthesis, indicating a role for LIGHT in the regulation of IFN-γ and as a putative mediator of proinflammatory T-T interactions in the intestinal mucosa. Taken together, these findings suggest LIGHT-herpesvirus entry mediator mediated signaling as an important immune regulatory mechanism in mucosal inflammatory responses.

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Section: Characterization Of Light-expressing T Cell Subsets In Peripmentioning

confidence: 99%

LIGHT Expression by Mucosal T Cells May Regulate IFN-γ Expression in the Intestine

Cohavy

Zhou

Granger

et al. 2004

The Journal of Immunology

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“…CD40L is a cell surface molecule involved in the initiation of the T cell immune response 16,17 in the induction of antigen-presenting cell maturation and in B cell activation, [16][17][18][19] while IL2 is a secreted molecule essential for T cell expansion during the immune response. 20,21 CD40L-and IL2-Ad5/F35 were used to infect both CD34 + and CD34 − lin − as described above.…”

Section: Expression Of Therapeutic Genes Using Ad5/f35mentioning

confidence: 99%

Efficient infection of primitive hematopoietic stem cells by modified adenovirus

et al. 2001

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Almost all studies of adenoviral vector-mediated gene transfer have made use of the adenovirus type 5 (Ad5). Unfortunately, Ad5 has been ineffective at infecting hematopoietic progenitor cells (HPC). Chimeric Ad5/F35 vectors that have been engineered to substitute the shorter-shafted fiber protein from Ad35 can efficiently infect committed hematopoietic cells and we now show highly effective gene transfer to primitive progenitor subsets. An Ad5GFP and Ad5/F35GFP vector was added to CD34 + and CD34 − lineage − (lin − ) HPC. Only 5-20% of CD34 + and CD34 − lin − cells expressed GFP after Ad5 exposure. In contrast, with the Ad5/F35 vector, 30-70% of the CD34 + , 50-70% of the CD34 − lin − and up to 60% of the CD38 − HPC expressed GFP and there was little evident cellular toxicity. Because of these improved results, we

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“…to efficiently reach the LP-DC, it is difficult to quantify how much anti-CD40 reaches the SI-LP. However, Diehl et al suggested that CD40-CD40L interactions lead to T-cell immunity in most systemic organ sites but to T-cell tolerance in mucosal sites [40]. Indeed, semimature phenotype of LP-DC did not change between 4 and 9 h after anti-CD40 treatment and this treatment failed to differentiate the Th1 cells toward oral Ag in vivo.…”

Section: and Cd8amentioning

confidence: 99%

Functional maturation of lamina propria dendritic cells by activation of NKT cells mediates the abrogation of oral tolerance

et al. 2008

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We previously showed that although systemic administration of a-galactosylceramide (aGalCer) or agonistic anti-CD40 induced functional maturation of dendritic cells (DC) in mesenteric lymph nodes, only the former treatment succeeded in breaking the induction of oral tolerance. In this study, we looked for the essential factor responsible for the disruption of oral tolerance. We found that lamina propria (LP)-DC was responsible for the oral OVA presentation and that Peyer's patch was not essential for the induction of oral tolerance. Therefore, we investigated the role of LP-DC. Treatment with aGalCer but not with anti-CD40 induced the full maturation of LP-DC at an early time point. This functional activation of LP-DC was mediated by strong activation of NKT cells that reside abundantly in the small intestinal lamina propria (SI-LP) and interferon-c partially contributed to the LP-DC activation. LP-DC isolated from aGalCer-treated OVA-fed mice induced the differentiation of naïve CD4 1 T cells into Th1 and Th2 and was associated with the reduced Foxp3 1 population. In contrast, LP-DC isolated from anti-CD40-treated OVA-fed mice failed to generate Th cell differentiation but induced more Foxp3 1 CD4 1 T cells. Our results demonstrate that triggered by NKT cells in SI-LP, functional maturation of Ag-capturing DC from SI-LP is necessary for the abrogation of oral tolerance induction.

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The role of CD40 in peripheral T cell tolerance and immunity

Cited by 68 publications

References 66 publications

LIGHT Expression by Mucosal T Cells May Regulate IFN-γ Expression in the Intestine

LIGHT Expression by Mucosal T Cells May Regulate IFN-γ Expression in the Intestine

Efficient infection of primitive hematopoietic stem cells by modified adenovirus

Functional maturation of lamina propria dendritic cells by activation of NKT cells mediates the abrogation of oral tolerance

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