scholarly journals Human colonic intraepithelial lymphocytes regulate the cytokines produced by lamina propria mononuclear cells

1997 ◽  
Vol 6 (2) ◽  
pp. 105-109 ◽  
Author(s):  
P. Hoang ◽  
J. P. Dehennin ◽  
Li Li ◽  
C. Sibille ◽  
A. Geubel ◽  
...  
Keyword(s):  
Lamina Propria ◽  
Mononuclear Cells ◽  
Interleukin 2 ◽  
Cell Interaction ◽  
Interferon Γ ◽  
Intraepithelial Lymphocytes ◽  
Lamina Propria Mononuclear Cells ◽  
Transwell Filter

Using anin vitroautologous human system, the immunomodulatory function of colonic intraepithelial lymphocytes (IEL) on cytokine production by lamina propria mononuclear cells (LPMNC) has been investigated. In contrast to LPMNC, colonic IEL produced only low amounts of IL-10, interferon-γ and interleukin-2. However, co-culture experiments (IEL + LPMNC) have shown that IEL can enhance the PHA-induced synthesis of IL-2 and interferon-γ, but not IL-10 by LPMNC. Using a transwell filter culture system apparatus, this effect was shown not to require a cell-to-cell interaction. Thus, IELin vitromay modulate the cytokine synthesis of LPMNC, through the production of soluble factors. This may prove highly relevant in thein vivoimmune activation of the gastrointestinal mucosa.

scholarly journals Spontaneous secretion of interferon γ and interleukin 4 by human intraepithelial and lamina propria gut lymphocytes

Gut ◽  
1998 ◽  
Vol 42 (5) ◽  
pp. 643-649 ◽  
Author(s):  
M Carol ◽  
A Lambrechts ◽  
A Van Gossum ◽  
M Libin ◽  
M Goldman ◽  
...  
Keyword(s):  
Lamina Propria ◽  
Intestinal Mucosa ◽  
Mononuclear Cells ◽  
Critical Role ◽  
Gastrointestinal Diseases ◽  
Interferon Γ ◽  
Interleukin 4 ◽  
Peripheral Blood Mononuclear ◽  
Ifn Γ

Background—Cytokines secreted by intestinal T lymphocytes probably play a critical role in regulation of the gut associated immune responses.Aims—To quantify interferon γ (IFN-γ) and interleukin 4 (IL-4) secreting cells (SC) among human intraepithelial (IEL) and lamina propria (LPL) lymphocytes from the duodenum and right colon in non-pathological situations and in the absence of in vitro stimulation.Patients—Duodenal and right colonic biopsy specimens were obtained from patients with no inflammation of the intestinal mucosa.Methods—Intraepithelial and lamina propria cell suspensions were assayed for numbers of cells spontaneously secreting IFN-γ and IL-4 by a two site reverse enzyme linked immunospot technique (ELISPOT).Results—The relatively high proportion of duodenal lymphocytes spontaneously secreting IFN-γ (IEL 3.6%; LPL 1.9%) and IL-4 (IEL 1.3%; LPL 0.7%) contrasted with the very low numbers of spontaneously IFN-γ SC and the absence of spontaneously IL-4 SC among peripheral blood mononuclear cells. In the basal state, both IFN-γ and IL-4 were mainly produced by CD4+ cells. Within the colon, only 0.2% of IEL and LPL secreted IFN-γ in the basal state, and 0.1% secreted IL-4.Conclusions—Compared with peripheral lymphocytes substantial proportions of intestinal epithelial and lamina propria lymphocytes spontaneously secrete IFN-γ and/or IL-4. These cytokines are probably involved in the normal homoeostasis of the human intestinal mucosa. Disturbances in their secretion could play a role in the pathogenesis of gastrointestinal diseases.

scholarly journals Effect of Coexpression of Interleukin-2 by Recombinant Respiratory Syncytial Virus on Virus Replication, Immunogenicity, and Production of Other Cytokines

2000 ◽  
Vol 74 (15) ◽  
pp. 7151-7157 ◽  
Author(s):  
Alexander Bukreyev ◽  
Stephen S. Whitehead ◽  
Calman Prussin ◽  
Brian R. Murphy ◽  
Peter L. Collins
Keyword(s):  
Respiratory Syncytial Virus ◽  
Mononuclear Cells ◽  
Protective Efficacy ◽  
Interleukin 2 ◽  
Cytokine Mrna ◽  
Virus Growth ◽  
Ifn Γ ◽  
Syncytial Virus

ABSTRACT We constructed rRSV/mIL-2, a recombinant respiratory syncytial virus (rRSV) containing the coding sequence of murine interleukin-2 (mIL-2) in a transcription cassette inserted into the G-F intergenic region. The recovered virus (rRSV/mIL-2) expressed high levels (up to 2.8 μg/ml) of mIL-2 in cell culture. Replication of rRSV/mIL-2 in vitro was reduced up to 13.6-fold from that of wild-type (wt) rRSV, an effect that was due to the presence of the foreign insert but was not specific to mIL-2. Replication of the rRSV/mIL-2 virus in the upper and lower respiratory tracts of BALB/c mice was reduced up to 6.3-fold, an effect that was specific to mIL-2. The antibody response, including the levels of RSV-specific serum immunoglobulin G1 (IgG1), IgG2a, IgA, and total IgG, and the level of protective efficacy against wt RSV challenge were not significantly different from those of wt rRSV. Analysis of total pulmonary cytokine mRNA isolated 1 and 4 days following infection with rRSV/mIL-2 revealed elevated levels of mRNA for IL-2, gamma interferon (IFN-γ), IL-4, IL-5, IL-6, IL-10, IL-13, and IL-12 p40 compared to those for wt rRSV. Flow cytometry of total pulmonary mononuclear cells isolated 10 days following infection with rRSV/mIL-2 revealed increased levels of CD4+ T lymphocytes expressing either IFN-γ or IL-4 compared to those of wt rRSV. These elevations in cytokine mRNA or cytokine-expressing CD4+cells relative to those of wt rRSV-primed animals were not observed following challenge with wt RSV on day 28. Thus, the expression of mIL-2 by rRSV was associated with a modest attenuation of virus growth in vivo, induction of serum antibodies at levels comparable to that of wt rRSV, and transient increases in both the Th1 and Th2 CD4+ lymphocytes and cytokine mRNAs compared to those of wt rRSV.

CD49d provides access to “untouched” human Foxp3+ Treg free of contaminating effector cells

Blood ◽  
2009 ◽  
Vol 113 (4) ◽  
pp. 827-836 ◽  
Author(s):  
Markus Kleinewietfeld ◽  
Mireille Starke ◽  
Diletta Di Mitri ◽  
Giovanna Borsellino ◽  
Luca Battistini ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Treg Cells ◽  
Interferon Γ ◽  
Clinical Applications ◽  
Interleukin 17 ◽  
Peripheral Blood Mononuclear ◽  
Effector Cells ◽  
Ifn Γ

Abstract The adoptive transfer of regulatory Foxp3+ T (Treg) cells has been shown in various animal models to prevent inflammatory immune and autoimmune diseases. Translation into therapeutic applications, however, is hindered by the lack of suitable techniques and markers. CD25, commonly used to isolate Treg cells from mice, has only limited value in humans as it is also present on proinflammatory CD4+ effector cells. Here we show that clean populations of human Foxp3+ Treg cells can be obtained with antibodies directed against CD49d. The marker is present on proinflammatory peripheral blood mononuclear cells but is absent on immune-suppressive Treg cells. Depletion with α-CD49d removes contaminating interferon-γ (IFN-γ)– and interleukin-17 (IL-17)–secreting cells from Treg preparations of CD4+CD25high cells. More importantly, in combination with α-CD127 it allows the isolation of “untouched” Foxp3+ Treg (ie, cells that have not been targeted by an antibody during purification). The removal of CD49d+/CD127+ cells leaves a population of Foxp3+ Treg virtually free of contaminating CD25+ effector cells. The cells can be expanded in vitro and are effective suppressors both in vitro and in vivo. Thus, CD49d provides access to highly pure populations of untouched Foxp3+ Treg cells conferring maximal safety for future clinical applications.

scholarly journals Autologous Tumor Infiltrating T Cells Cytotoxic for Follicular Lymphoma Cells Can Be Expanded In Vitro

Blood ◽  
1997 ◽  
Vol 89 (10) ◽  
pp. 3806-3816 ◽  
Author(s):  
Joachim L. Schultze ◽  
Mark J. Seamon ◽  
Sabine Michalak ◽  
John G. Gribben ◽  
Lee M. Nadler
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Cytotoxic T Cells ◽  
Interleukin 2 ◽  
Interferon Γ ◽  
Autologous Tumor

Abstract Follicular lymphomas (FLs) rarely induce clinically significant T-cell–mediated responses. We showed that freshly isolated tumor infiltrating T cells (T-TILs) lack tumor-specific cytotoxicity. Stimulation of these T cells with FL cells in the presence of interleukin-2 (IL-2) and/or costimulation via CD28 does not lead to T-cell activation and expansion. In contrast, when stimulated with FL cells preactivated via CD40, autologous T-TILs can be expanded by the addition of exogenous IL-2. These T cells can be further expanded in vitro by the addition of exogenous IL-4, IL-7, or interferon-γ, but not IL-12. Once activated, these T cells showed FL-directed cytotoxicity in four of five patients tested. We concluded that autologous cytotoxic anti-FL–specific T cells exist, but can only be detected in vitro under optimized conditions for T-cell stimulation and expansion. This suggests that their frequency in vivo is either very low or that the microenvironment does not provide the necessary signals to activate these T cells. This model system allows dissection of the requisite conditions for activation and expansion of lymphoma-directed cytotoxicity and may permit expansion of previously activated cytotoxic T cells for adoptive transfer.

scholarly journals In vitro and in vivo immunomodulatory effects of anti-Pneumocystis carinii drugs.

1996 ◽  
Vol 40 (5) ◽  
pp. 1294-1297 ◽  
Author(s):  
M Viora ◽  
A De Luca ◽  
A D'Ambrosio ◽  
A Antinori ◽  
E Ortona
Keyword(s):  
Mononuclear Cells ◽  
Nk Cell ◽  
Human Peripheral Blood ◽  
Pneumocystis Carinii ◽  
Interleukin 2 ◽  
Cell Activity ◽  
Peripheral Blood Mononuclear ◽  
T Lymphocyte Proliferation

The anti-Pneumocystis carinii drug effects on mitogen-, antigen-, and interleukin-2-induced proliferative responses and on natural killer (NK) cell-mediated activity were analyzed in vivo (rats) and in vitro (normal human peripheral blood mononuclear cells). Splenocytes derived from in vivo piritrexim- and clindamycin-treated rats showed a significant inhibition of mitogen-induced proliferative responses. In vitro exposure to clindamycin, piritrexim, and pyrimethamine caused an inhibition of human T lymphocyte proliferation in response to mitogen, antigen, and interleukin-2 stimulation. Rat NK cell-mediated cytotoxic activity was not affected by the drugs, and human NK cell activity was reduced only at the highest concentration (10 micrograms/ml) of the drugs. The potential immunotoxicity of the long-term administration of these agents in humans needs further investigation.

Interleukin-2 activity of colonic lamina propria mononuclear cells in a rat model of experimental colitis

1993 ◽  
Vol 104 (4) ◽  
pp. 964-972 ◽  
Author(s):  
Covadonga Gurbindo ◽  
Pierre Russo ◽  
Sidney Sabbah ◽  
Marie-Jeanne Lohoues ◽  
Ernest Seidman
Keyword(s):  
Lamina Propria ◽  
Rat Model ◽  
Mononuclear Cells ◽  
Interleukin 2 ◽  
Experimental Colitis ◽  
Lamina Propria Mononuclear Cells

scholarly journals Efficient gene delivery to the inflamed colon by local administration of recombinant adenoviruses with normal or modified fibre structure

Gut ◽  
1999 ◽  
Vol 44 (6) ◽  
pp. 800-807 ◽  
Author(s):  
S Wirtz ◽  
P R Galle ◽  
M F Neurath
Keyword(s):  
Gene Expression ◽  
Gene Delivery ◽  
Lamina Propria ◽  
Reporter Gene ◽  
Mononuclear Cells ◽  
Reporter Gene Expression ◽  
Local Administration ◽  
Fibre Structure

BACKGROUND/AIMSReplication deficient recombinant adenoviruses represent an efficient means of transferring genes in vivo into a wide variety of dividing and quiescent cells from many different organs. Although the gastrointestinal tract is a potentially attractive target for gene therapy approaches, only a few studies on the use of viral gene transfer vehicles in the gut have been reported. The prospects of using recombinant adenoviruses for gene delivery into epithelial and subepithelial cells of the normal and inflamed colon are here analysed.METHODSAn E1/E3 deleted recombinant adenovirus (denoted AdCMVβGal) and an adenovirus with modified fibre structure (denoted AdZ.F(pk7)) both expressing the bacterial lacZ gene under the control of a human cytomegalovirus promoter were used for reporter gene expression in vitro and in vivo. β-Galactosidase activity was determined by specific chemiluminescent reporter gene assay.RESULTSIntravenous or intraperitoneal injection of AdCMVβGal into healthy Balb/c mice caused strong reporter gene expression in the liver and spleen but not in the colon. In contrast, local administration of AdCMVβGal resulted in high reporter gene expression in colonic epithelial cells and lamina propria mononuclear cells. A local route of adenovirus administration in mice with experimental colitis induced by the hapten reagent trinitrobenzenesulphonic acid was next evaluated. Interestingly, rectal administration of AdCMVβGal caused a higher β-galactosidase activity in isolated lamina propria cells from infected mice with experimental colitis than in those from controls. Furthermore, isolated lamina propria cells from mice with colitis infected in vitro showed a significant increase in reporter gene activity compared with controls. Finally, AdZ.F(pk7) adenoviruses with modified fibre structure produced 10- to 40-fold higher reporter gene activity in spleen T cells and lamina propria mononuclear cells of colitic mice compared with standard AdCMVβGal vectors.CONCLUSIONSLocal administration of recombinant adenoviruses with normal or modified fibre structure could provide a new reliable method for targeted gene expression in the inflamed colon. Such gene delivery could be used to specifically express signal transduction proteins with therapeutic potential in inflamed colonic tissue. In particular, adenoviruses with modified fibre structure may be useful in T cell directed therapies in intestinal inflammation.

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