Anti-CD2 and anti-CD3 induced T cell cytotoxicity of human intraepithelial and lamina propria lymphocytes.

Rüthlein, J; Heinze, Gabriele; Auer, I. O.

doi:10.1136/gut.33.12.1626

Cited by 23 publications

(11 citation statements)

References 37 publications

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“…Our results are consistent with previous reports which show that human IEL exert spontaneous cytotoxicity against tumour target cells [13,17]. On the other hand, it is reported that human IEL exhibit cytotoxicity only after in vitro activation with mitogens, IL-2 [18], or ligation of CD2 and CD3 [19]. In these studies, the cytotoxic function was evaluated by 51 Crrelease assay, which may be less sensitive in detecting Fas-FasLmediated cytotoxicity compared with the 3 H-thymidine release assay used in this study.…”

Section: Discussionsupporting

confidence: 93%

Functional expression of Fas and Fas ligand on human intestinal intraepithelial lymphocytes

Morimoto

Hizuta

Ding

et al. 1999

Clinical and Experimental Immunology

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Intestinal intraepithelial lymphocytes (IEL) constitute the first lymphoid compartment to encounter dietary antigens and intestinal pathogens. IEL are proposed to be involved in the defence against bacterial and viral invasion and to play an important role in mucosal immunity. Fas (CD95/APO-1) is a surface receptor that induces apoptotic cell death upon ligation with Fas ligand (FasL). The aim of this study was to examine the expression and function of Fas and FasL on freshly isolated normal human colonic IEL. The expression and function of Fas and FasL on IEL isolated from 40 normal colonic specimens were examined by flow cytometry, reverse transcriptase-polymerase chain reaction, immunohistochemistry, and DNA-release cytotoxicity assay. Virtually all CD3+ IEL (95.2 +/- 4.3%) expressed Fas and were sensitive to agonistic anti-Fas antibody, whereas only 56.6 +/- 8.4% of peripheral T lymphocytes expressed Fas and were resistant to the antibody. We also detected FasL mRNA and protein (40.1 +/- 4.2%) on IEL, and found that IEL exerted FasL-mediated cytotoxicity against Fas-expressing target cells. These findings suggest that human IEL are activated in situ but are tightly regulated by the constitutive expression of functional Fas and FasL to maintain homeostasis of the mucosal immune system.

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Section: Discussionsupporting

confidence: 93%

Functional expression of Fas and Fas ligand on human intestinal intraepithelial lymphocytes

Morimoto

Hizuta

Ding

et al. 1999

Clinical and Experimental Immunology

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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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“…IELs play an important role in protection from epithelial tumor cells through their function as cytolytic agents (37). Lamina propria lymphocytes (LPLs), also mainly T cells, are derived from the thymus; they constitute primarily the ␣␤ form of the TCR (12) and have some cytolytic activity against tumor cell lines (38). CD8 T lymphocytes, compromising two subpopulations of ␣-and ␤-chain phenotypes, have cytolytic functions and are found in both the intraepithelial and lamina propria regions (4).…”

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confidence: 99%

Adrenalectomy in mice does not prevent loss of intestinal lymphocytes after exercise

Hoffman‐Goetz

Quadrilatero

Boudreau

et al. 2004

Journal of Applied Physiology

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Exhaustive exercise is associated with an increase in circulating glucocorticoids (GCs), lymphocyte apoptosis, and a reduction in intestinal lymphocyte number. The present study examined the role of GCs on the numerical changes seen in intestinal lymphocytes after exercise. Female C57BL/6 mice were bilaterally adrenalectomized (ADX; n ϭ 18) or given sham surgery (Sham; n ϭ 18) and assigned to one of three exercise conditions: treadmill running (28 m/min, 90 min, 2°slope) and killed immediately or after 24 h recovery, or not exercised and killed immediately after 90-min exposure to the treadmill environment. Lymphocytes were isolated from the intestines with CD45 ϩ cells collected by positive selection using magnetic bead separation columns, and lymphocyte subpopulations were analyzed by flow cytometry for CD45 ϩ , CD3␣␤ ϩ , CD3␥␦ ϩ , CD8␤ ϩ , CD8␣ ϩ , CD4 ϩ , and NK ϩ phenotypic markers. ADX mice had significantly more intestinal CD45 ϩ leukocytes (P Ͻ 0.05) and CD3␣␤ ϩ (P Ͻ 0.05), CD3␥␦ ϩ (P Ͻ 0.01), CD8␣ ϩ (P Ͻ 0.001), and NK ϩ (P Ͻ 0.05) intestinal lymphocytes than Sham mice. There was a significant effect of exercise condition on total intestinal CD45 ϩ leukocytes (P Ͻ 0.01) and CD3␣␤ ϩ (P Ͻ 0.05), CD8␣ ϩ (P Ͻ 0.001), and CD4 ϩ (P Ͻ 0.05) intestinal lymphocytes, with fewer cells at 24 h postexercise compared with the other treatment conditions. There were no surgical ϫ exercise interaction effects on the CD3 and CD8 phenotype numbers. Plasma corticosterone was virtually nil in ADX mice regardless of exercise condition but was significantly elevated in Sham mice immediately postexercise (P Ͻ 0.001). The data indicate that ADX does not prevent the loss of lymphocytes from the intestinal mucosa 24 h after strenuous exercise and GCs are not directly causal in the leukopenia of exercise. treadmill running; adrenal glands; glucocorticoids NUMEROUS STUDIES HAVE SHOWN that acute exercise is associated with induction of apoptosis or programmed cell death and loss of lymphocytes from blood, thymus, and spleen in humans and laboratory animals (9,20,28,29). Lymphocyte loss and/or apoptosis have been observed in other situations characterized by extreme physiological stress, including burn injury (15), electrical shock (48), and chronic restraint stress (42), and may reflect release of stress hormones, in particular glucocorticoids (GCs). GCs trigger apoptosis in lymphocytes by acting on an intracellular pathway via the mitochondria (2), which results in the accumulation of mitochondrial derived cytochrome c within the cytosol, loss of mitochondrial membrane integrity, externalization of phosphatidylserine at cell membranes, and DNA fragmentation (27,45).The intestinal intraepithelial lymphocytes (IELs) are a unique population of T cells that function as a first line of defense against exogenous pathogens, many of which develop independently of the thymus gland [i.e., T cells with the ␥␦ form of the T cell receptor (TCR)] (35). IELs play an important role in protection from epithelial tumor cells through their function a...

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Anti-CD2 and anti-CD3 induced T cell cytotoxicity of human intraepithelial and lamina propria lymphocytes.

Abstract: The effector function of immunocompetent cells in the gut mucosa has not yet been defined. The Changes in cell mediated cytotoxicity of intraepithelial lymphocytes and lamina propria lymphocytes may be involved in the mucosal damage in these inflammatory conditions.

Cited by 23 publications

References 37 publications

Functional expression of Fas and Fas ligand on human intestinal intraepithelial lymphocytes

Functional expression of Fas and Fas ligand on human intestinal intraepithelial lymphocytes

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

Adrenalectomy in mice does not prevent loss of intestinal lymphocytes after exercise

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