Interferon β decreases T cell activation and interferon γ production in multiple sclerosis

Activated T cells are able to stimulate proliferation in resting T cells through an antigen non-specific mechanism. The in vivo usefulness of this T cell-T cell activation is unclear, but it may serve to amplify immune responses. T cell-T cell activation could be involved in the well-documented occurrence of multiple sclerosis (MS) exacerbations following viral infections. Excessive activation via this pathway could also be a factor in the etiology of MS. We tested the hypothesis that excessive T cell-T cell activation occurs in MS patients using in vitro proliferation assays comparing T cells from MS patients to T cells from controls. When tested as responder cells, T cells from MS patients proliferated slightly less after stimulation with previously activated cells than T cells from controls. When tested as stimulator cells, activated cells from MS patients stimulated slightly more non-specific proliferation than activated cells from controls. Neither of these differences were statistically significant We conclude that T cell proliferation in response to activated T cells is similar in MS and controls.

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Molecular transfer of CD40 and OX40 ligands to leukemic human B cells induces expansion of autologous tumor–reactive cytotoxic T lymphocytes

Blood ◽

10.1182/blood-2004-07-2556 ◽

2005 ◽

Vol 105 (6) ◽

pp. 2436-2442 ◽

Cited By ~ 42

Author(s):

Ettore Biagi ◽

Gianpietro Dotti ◽

Eric Yvon ◽

Edward Lee ◽

Martin Pule ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

T Cell Activation ◽

Cell Activation ◽

Antibody Therapy ◽

Interferon Γ ◽

Lymphocytic Leukemia ◽

Cytotoxic T Cell ◽

Autologous Tumor ◽

Molecular Transfer

AbstractClinical benefits from monoclonal antibody therapy for B-chronic lymphocytic leukemia (B-CLL) have increased interest in developing additional immunotherapies for the disease. CD40 ligand is an accessory signal for T-cell activation and can overcome T-cell anergy. The OX40-OX40 ligand pathway is involved in the subsequent expansion of memory antigen-specific T cells. We expressed both CD40L and OX40L on B-CLL cells by exploiting the phenomenon of molecular transfer from fibroblasts overexpressing these ligands. We analyzed the effects of the modified B-CLL cells on the number, phenotype, and cytotoxic function of autologous T cells in 7 B-CLL patients. Transfer of CD40L and OX40L was observed in all and was followed by the up-regulation of B7-1 and B7-2. The culture of CD40L/OX40L-expressing B-CLL cells with autologous T cells generated CD4+/CD8+ cytotoxic T-cell lines, which secreted interferon-γ (IFN-γ) and granzyme-B/perforin in response to autologous, but not to allogeneic, B-CLL cells or to autologous T-cell blasts. CD40L or OX40L alone was insufficient to expand tumor-reactive T cells. The combination of CD40L and OX40L on B-CLL cells may allow the generation of therapeutic immune responses to B-CLL, either by active immunization with modified tumor cells or by adoptive immunotherapy with tumor-reactive autologous T cells.

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Areca nut extract suppresses T-cell activation and interferon-γ production via the induction of oxidative stress

Food and Chemical Toxicology ◽

10.1016/j.fct.2007.02.005 ◽

2007 ◽

Vol 45 (8) ◽

pp. 1410-1418 ◽

Cited By ~ 27

Author(s):

C.C. Wang ◽

T.Y. Liu ◽

S.P. Wey ◽

F.I. Wang ◽

T.R. Jan

Keyword(s):

Oxidative Stress ◽

T Cell ◽

T Cell Activation ◽

Cell Activation ◽

Interferon Γ ◽

Areca Nut

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Intravenous immunoglobulins suppress T-cell priming by modulating the bidirectional interaction between dendritic cells and natural killer cells

Blood ◽

10.1182/blood-2007-03-077057 ◽

2007 ◽

Vol 110 (9) ◽

pp. 3253-3262 ◽

Cited By ~ 57

Author(s):

Thanyalak Tha-In ◽

Herold J. Metselaar ◽

Hugo W. Tilanus ◽

Zwier M. A. Groothuismink ◽

Ernst J. Kuipers ◽

...

Keyword(s):

Dendritic Cells ◽

T Cell ◽

Nk Cells ◽

T Cell Activation ◽

Cell Activation ◽

Nk Cell ◽

Intravenous Immunoglobulins ◽

Interferon Γ ◽

T Cell Priming ◽

Induced Apoptosis

AbstractThe modes of action of intravenous immunoglobulins (IVIgs) in exerting their immunomodulatory properties are broad and not fully understood. IVIgs can modulate the function of various immune cells, including suppressing the capacity of dendritic cells (DCs) to stimulate T cells. In the present study, we showed that DCs matured in the presence of IVIgs (IVIg-DCs) activated NK cells, and increased their interferon-γ production and degranulation. The activated NK cells induced apoptosis of the majority of IVIg-DCs. In consequence, only in the presence of NK cells, IVIg-DCs were 4-fold impaired in their T-cell priming capacity. This was due to NK-cell–mediated antibody-dependent cellular cytotoxicity (ADCC) to IVIg-DCs, probably induced by IgG multimers, which could be abrogated by blockade of CD16 on NK cells. Furthermore, IVIg-DCs down-regulated the expression of NKp30 and KIR receptors, and induced the generation of CD56brightCD16−CCR7+ lymph node–type NK cells. Our results identify a novel pathway, in which IVIgs induce ADCC of mature DCs by NK cells, which downsizes the antigen-presenting pool and inhibits T-cell priming. By influencing the interaction between DCs and NK cells, IVIgs modulate the ability of the innate immunity to trigger T-cell activation, a mechanism that can “cool down” the immune system at times of activation.

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Increased state of activation of CD4 positive T cells and elevated interferon γ production in pouchitis

Gut ◽

10.1136/gut.43.4.499 ◽

1998 ◽

Vol 43 (4) ◽

pp. 499-505 ◽

Cited By ~ 59

Author(s):

A Stallmach ◽

F Schäfer ◽

S Hoffmann ◽

S Weber ◽

I Müller-Molaian ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

T Cell Activation ◽

Cell Activation ◽

Mononuclear Cells ◽

Interferon Γ ◽

Ileoanal Pouch ◽

T Cell Subsets ◽

Activation Markers ◽

Ifn Γ

Background—Immunoregulatory abnormalities of T cells might be of importance in the pathogenesis of pouchitis after ileoanal pouch anastomosis (IAP).Aims—To characterise T cell subsets, their state of activation, and production of cytokines in inflamed and non-inflamed pouches in patients with ulcerative colitis (UC) and familial adenomatous polyposis (FAP). The influence of T cell activation on mucosal transformation was also studied.Patients—Mucosal biopsy specimens were taken from 42 patients with IAP (33 with UC and nine with FAP).Methods—Mononuclear cells were isolated by standard techniques and characterised by three colour flow cytometry. Interferon γ (IFN-γ) production was studied using the ELISPOT technique.Results—In patients with UC with pouchitis there was a significant increase in the CD4:CD8 ratio, expression of activation markers on CD3+ cells, and number of IFNγ producing mononuclear cells compared with patients with UC without pouchitis (CD4:CD8 ratio 1.3 (range 0.7–2.7) versus 0.6 (0.1–1.0), p=0.012). In addition, a positive correlation between increased crypt depth and the number of CD4+ cells (r=0.57) was shown.Conclusion—The observed increase in activated mucosal CD4+ T cells and IFN-γ production might lead to mucosal destruction and crypt hyperplasia as seen in pouchitis.

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