Human mucosal T-cell cytotoxicity

Shanahan, Fergus; Deem, Richard L.; Nayersina, Ramin; Leman, Bernard; Targan, Stephan R.

doi:10.1016/0016-5085(88)90554-9

Cited by 39 publications

(7 citation statements)

References 35 publications

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“…Verification of the amount of cells killed by C lysis with anti-CD3 revealed that approximately one third of LPMC were lysed which represents the percentage of T cells present in the lamina propria as reported by others [4,21]. However, lamina propria T cells can be involved in non-MHC-restricted killing by pretreating them with anti-CD3 antibodies as shown by Shanahan et al [27]. In our view, their study describes another mechanism of cell-mediated cytotoxicity than the spontaneous killing of tumor cells, we report here, since they mimicked the in vivo activation of T cells primed by environmental antigenic stimuli.…”

Section: Discussionmentioning

confidence: 58%

The CD56 adhesion molecule is the major determinant for detecting non‐major histocompatibility complex‐restricted cytotoxic mononuclear cells from the intestinal lamina propria

et al. 1992

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In this study, specific antibodies against natural killer (NK) cell surface markers identify these cells to be commonly present in normal intestinal mucosa of inflammatory bowel disease (IBD) and carcinoma patients. Cells expressing the CD56 adhesion molecule were found to be far more abundant than CD16+ cells. Functional studies revealed that cells mediating non-major histocompatibility complex-restricted cytotoxicity (NK activity) in the lamina propria express the CD56 surface antigen, whereas only a minority of this activity resides in the population with CD16 expression. This is in contrast with peripheral blood NK cells, which were found to be almost exclusively both CD16+ and CD56+. Moreover, in the lamina propria of the intestine we found CD3+ T lymphocytes not to be involved in spontaneous cell-mediated killing of tumor cells. Considerably higher numbers of cells with the CD16 or CD56 surface markers were found to be present in normal mucosa of IBD patients compared with normal mucosa of carcinoma patients, which was also reflected in higher levels of cytotoxicity detected in lamina propria mononuclear cell preparations from normal IBD mucosa. Because of the disease-related localization of the mucosa studied from both patient groups, i.e. ileum vs. colon, the observed differences may be related to tissue characteristics. Within the IBD group, relatively high levels of cytotoxicity were found in cell preparations from normal mucosa of Crohn's disease patients compared with ulcerative colitis patients, which might support the current concept that Crohn's disease affects the whole of the gastrointestinal tract.

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Section: Discussionmentioning

confidence: 58%

The CD56 adhesion molecule is the major determinant for detecting non‐major histocompatibility complex‐restricted cytotoxic mononuclear cells from the intestinal lamina propria

et al. 1992

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“…Recently, it has been shown that murine intestinal CD8+ TEL express the y/6-type heterodimer of the T-cell receptor (TcRI) (Goodman & Lefrancois, 1988;Bonneville et al, 1988), and mediate cytotoxicity following activation with anti-CD3 antibody (Goodman & Lefrancois, 1988). Human colonic TEL have also been shown to be capable of mediating cytolysis after anti-CD3 activation (Shanahan et al, 1988). On the basis of CD3-activated cytotoxicity and expression of TcR I, it has been postulated that TEL are primitive or immature cells which are not MHC restricted (Janeway, 1988;Janeway, Jones & Hayday, 1988).…”

Section: Introductionmentioning

confidence: 99%

Expression of T cell receptors TcR1 (gamma/delta) and TcR2 (alpha/beta) in the human intestinal mucosa

Trejdosiewicz

Smart

Oakes

et al. 1990

Advances in Mucosal Immunology

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Cryostat sections of normal human adult gastrointestinal mucosae were studied by double-label immunofluorescence with antibodies to CD3, CD4, CD8, CD5 and CD6, in parallel with antibodies fF1 and TCR61 against fl-chains and 6-chains of the T-cell receptor (TcR) types TcR2 (a/f) and TcRl (y/6), respectively. Virtually no TcRl + were found within the lamina propria. In the epithelial compartment, TcR1 + cells were infrequent: in the small bowel, -2% of T cells were TcR1 + . In the colonic epithelium, the percentage of T cells expressing y/6-chains was higher, with a mean value approximating 15-20%, although this apparently large percentage increase compared with small bowel reflects in part a much lower density ofcolonic IEL, as absolute numbers ofTCRbI + cells were comparable. Of the TcRl + population, about half were CD4-CD8-'double negatives' and the remainder were CD8+. TcRl + cells were also CD5-CD6-, irrespective of expression of CD8. No CD4+ cells expressing TcRl were observed: essentially all CD4+ cells were fF1+, with some variability of labelling intensity. Approximately 30-50% of the CD8+ subset expressed the PF1 antigen strongly. However, in the remaining TcRl -CD8+ cells, which were all of the CD5-CD6phenotype, expression of the flF1 antigen was only detectable when streptavidin and biotin conjugates were used for amplification of labelling. Thus, the CD8+ CD5subset, a prominent population of the epithelial compartment of the small bowel, was either TcR2dUII in the majority or TcRl + in a minority. Our data imply that y/6 TcRl cells may be actively excluded from intestinal lamina propria, and that any preferential localization that does occur is limited and is rather a feature of the colonic mucosa, rather than the small bowel.

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“…An indirect approach takes advantage ofthe fact that MoAbs specific for the T cell receptor (TCR)/CD3 complex can induce antigen-independent cytotoxicity of in vivo primed CTL [7]. Patients with IBD have an apparent increase in anti-CD3-triggered CTL in peripheral blood, suggesting a change in immune activity [8]; however, the nature of this activity in mucosal T cells of CD patients is not clear [9,10].…”

Section: Introductionmentioning

confidence: 99%

Cytotoxic activity of Vβ8+ T cells in Crohn's disease: the role of bacterial superantigens

Baca-Estrada

Wong

Croitoru

1995

Clinical and Experimental Immunology

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SUMMARYIn Crohn's disease, disease-related stimuli could alter the T cell receptor (TCR) repertoire. To examine the possibility that changes in function may occur in T cell subsets without obvious changes in expression of TCR, we analysed the TCR repertoire of cytotoxic T lymphocytes in Crohn's disease peripheral blood. Furthermore, we examined the effect of bacterial superantigens, staphylococcal enterotoxin B (SEB) and E (SEE) on the cytotoxic function of T cell subsets bearing different TCR V genes using MoAbs specific for CD3 and TCR V gene products in a redirected cytotoxicity assay. There was no difference between patients and controls in the cytotoxicity measured in concanavalin A (Con A)-stimuiated peripheral blood mononuclear celts (PBMC) with anti-CD3 or with six of seven anti-TCR V gene MoAbs. However, the cytotoxicity of \3^ T cells was decreased in Crohn's disease patients. This was not due to a decrease in total or CD8 ^ T cells expressing V/38. Furthermore, in normal subjects, PBMC stimulation with SEE and SEB selectively expanded and increased the cytotoxicity of V/?8 and V/312 T cells, respectively. In Crohn's disease, although SEB stimulation increased the number and cytolytic function of the V/312 subset, SEE stimulation failed to increase cytolytic activity of V/38^ T cells in spile of the expansion of V/38^ Tceils. These results suggest that the changes in cytotoxic function observed in V/38 T cells in Crohn's patients may reflect previous exposure to a V/58-seIective superantigen.

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Human mucosal T-cell cytotoxicity

Cited by 39 publications

References 35 publications

The CD56 adhesion molecule is the major determinant for detecting non‐major histocompatibility complex‐restricted cytotoxic mononuclear cells from the intestinal lamina propria

The CD56 adhesion molecule is the major determinant for detecting non‐major histocompatibility complex‐restricted cytotoxic mononuclear cells from the intestinal lamina propria

Expression of T cell receptors TcR1 (gamma/delta) and TcR2 (alpha/beta) in the human intestinal mucosa

Cytotoxic activity of Vβ8+ T cells in Crohn's disease: the role of bacterial superantigens

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