Human mucosal cytotoxic effector cells

Shanahan, Fergus; Brogan, Michael; Targan, Stephan R.

doi:10.1016/0016-5085(87)90629-9

Cited by 47 publications

(14 citation statements)

References 31 publications

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“…LPMC were isolated from the resection samples by a technique modified from that described previously (25). Briefly, the intestinal specimen was washed with HBSS, and the mucosae were dissected away from the underlying layers.…”

Section: Purification Of Lpmcmentioning

confidence: 99%

Mucosa-Specific Targets for Regulation of IFN-γ Expression: Lamina Propria T Cells Use Differentcis-Elements than Peripheral Blood T Cells to Regulate Transactivation of IFN-γ Expression

Gonsky

Deem

Bream

et al. 2000

The Journal of Immunology

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Activation of lamina propria (LP) T cells via the CD2 pathway enhances IFN-γ (IFN-γ) secretion with further enhancement after CD28 coligation. The molecular mechanisms regulating IFN-γ expression in LP T cells remain unknown. Previous studies in PBL and T cell lines identified cis- and trans-regulatory elements in TCR-mediated expression of IFN-γ. This study examines CD2 and PMA/ionophore-responsive IFN-γ promoter elements. Activation of LPMC via CD2-induced IFN-γ secretion and a parallel up-regulation of mRNA expression. CD28 coligation enhanced mRNA stability without up-regulating transcription as measured by nuclear run-on. Transfection of a −2.7-kb IFN-γ promoter-reporter construct into PBL and LP mononuclear cells (LPMC) revealed significant promoter activity after CD2 activation, with additional transactivation after CD2/CD28 costimulation in PBL, but not in LPMC. Functional analysis using truncated promoter fragments identified distinct cis-regulatory regions selectively transactivating IFN-γ expression in PBL compared with LPMC. In PBL, CD2 activation elements reside within the −108- to +64-bp region. However, in LPMC the upstream region between −204 and −108 bp was essential. Transfection of the proximal and distal AP-1-binding elements, as well as TRE/AP-1 constructs, revealed functional activation of AP-1 subsequent to CD2 signaling, with activation critical in PBL but diminished in LPMC. Electromobility shift analysis using oligonucleotides encompassing the proximal, distal, and BED/AP-1-binding regions failed to demonstrate selective transactivation after CD2 signaling of LPMC. This report provides evidence that activation of LPMC results in transactivation of multiple promoter elements regulating IFN-γ expression distinct from those in PBL.

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Section: Purification Of Lpmcmentioning

confidence: 99%

Mucosa-Specific Targets for Regulation of IFN-γ Expression: Lamina Propria T Cells Use Differentcis-Elements than Peripheral Blood T Cells to Regulate Transactivation of IFN-γ Expression

Gonsky

Deem

Bream

et al. 2000

The Journal of Immunology

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show abstract

“…Most types ofcytotoxic cells and their function have been studied using the cells isolated from the IBD-involved mucosa, including natural killer cell activity, antibody-dependent cellular cytotoxicity, antigen specific T cell cytotoxicity, anti-CD3-induced cytotoxicity and lymphokine-activated killer (LAK) cell activity (3). Amongthese cytotoxic cells, LAKcell activity has been investigated intensively because of its broad activity against the target cells including those of intestinal origin (4)(5)(6)(7). Theconsistent and reliable nature of cytotoxic mechanisms can be used to reveal abnormalities of intestinal immunereactivity in IBD (7).…”

Section: Introductionmentioning

confidence: 99%

Lamina Propria Mononuclear Cells Express and Respond to Interleukin-2 Differently in Crohn's Disease and Ulcerative Colitis.

et al. 1996

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“…Cells with features of NK cells have also been identified in the lungs (42), gastrointestinal tract (43), and liver (44), but, at least in the liver, many of these are NKT cells (45). NK cells are not frequent in unstimulated lymph nodes, and unactivated NK cells do not circulate through the lymphatic system (46).…”

Section: Location Of Nk Cellsmentioning

confidence: 99%