Search results for "CD8"

JAK3/STAT5/6 Pathway Alterations Are Associated with Immune Deviation in CD8+ T Cells in Renal Cell Carcinoma Patients

2010

To investigate the molecular mechanisms underlying altered T cell response in renal cell carcinoma (RCC) patients, we compared autologous and allogeneic CD8(+) T cell responses against RCC line from RCC patients and their HLA-matched donors, using mixed lymphocyte/tumor cell cultures (MLTCs). In addition, we analyzed the expression of molecules associated with cell cycle regulation. Autologous MLTC responder CD8(+) T cells showed cytotoxic activity against RCC cell lines; however the analysis of the distribution of CD8(+) T-cell subsets revealed that allogenic counterparts mediate superior antitumor efficacy. In RCC patients, a decreased proliferative response to tumor, associated with defe…

Experimental confirmation of the 'protein traffic hypothesis' by routine diagnostic tests

2010

The 'protein traffic hypothesis' suggests that the inflammation associated with autoimmune disease, trauma and disturbances of blood circulation is the result of misguided protein trafficking. The hypothesis divides the antigen spectrum into an intracellular component and an extracellular component. While the intracellular component is recognised by MHC class-I molecules and is presented to CD8 T-lymphocytes, the extracellular component is recognised by MHC class-II molecules and is presented to CD4 T-lymphocytes. To test this hypothesis, CD4 and CD8 T-cell counts of 271 HIV-negative patients of the University Hospital, Mainz, Germany were examined retrospectively. The results corroborate t…

B7‐H1 and CD8+Treg: The enigmatic role of B7‐H1 in peripheral tolerance

2009

The interaction between B7-H1 (PD-L1) expressed on APC with PD-1 expressed by T cells was shown previously to result in inhibition of T-cell activation and autoimmune diseases. A paper in this issue of the European Journal of Immunology demonstrates that DC B7-H1 expression can in fact enhance autoimmunity, rather than suppress it. Using a model of direct injection of self antigen-loaded DC into the CNS, the authors demonstrate that DC with intact B7-H1 expression exacerbate CNS autoimmune disease. Importantly, the improved disease outcome in animals treated with B7-H1(-/-) DC is a result of a population of CD8(+) Treg cells that expand at the site of autoimmune inflammation.

Dynamic Antigen Presentation Patterns of Listeria monocytogenes-Derived CD8 T Cell Epitopes In Vivo

2001

Abstract Little information exists regarding the presentation of antigenic peptides in infected tissues. In this study the in vivo presentation of four different CD8 T cell epitopes of Listeria monocytogenes was monitored. Peptide presentation was measured by a new, highly sensitive, ex vivo Ag presentation assay that was based on the testing of freshly isolated cells from infected spleens with peptide-specific CD8 T cell lines in an IFN-γ-specific ELISPOT assay. Remarkably, the peptide presentation pattern of splenocytes and that of macrophages purified from spleens of L. monocytogenes-infected mice were different from those of in vitro infected macrophage-like cell lines. The in vivo Ag p…

Altered expression of nonclassical HLA class Ib antigens in human renal cell carcinoma and its association with impaired immune response

2003

Abstract An optimal antitumoral immune response requires the activation of both CD8 + and CD4 + T lymphocytes by the peptide antigen presentation via the human leukocyte antigen (HLA) class I and class II molecules, respectively. Downregulation or loss of HLA molecules has been found in human renal cell carcinoma (RCC) and provides a strategy of these tumors to evade T-cell mediated immunosurveillance. In addition, a tumor-specific upregulation of HLA-G has been recently described in RCC, which also leads to an impaired immune response. We here summarize the frequency of the constitutive and/or interferon-γ (IFN-γ) inducible expression of nonclassical HLA class Ib antigens in RCC cell lines…

Defective expression of CD95 (FAS/APO-1) molecule suggests apoptosis impairment of T and B cells in HLA-B8, DR3-positive individuals.

1997

Activation-induced apoptosis is one of the primary control mechanisms for the negative selection of an immune response, leading to maintenance of immune homeostasis and selective T cell deletion. The interaction between the surface molecule Fas and its ligand (FasL) has been proposed as a primary mechanism initiating T cell apoptosis. The T cell receptor modulates the expression and function of these molecules. Defects in the Fas/FasL apoptosis pathway have been shown to result in autoimmune disease in humans and in murine models. Because subjects carrying the HLA-B8, DR3 haplotype show a number of immune dysfunctions, including membrano-proliferative glomerulonephritis, systemic lupus eryt…

Anti-GD3 antibodies are potent activators of human gamma/delta and alpha/beta positive T cells.

1995

The ganglioside GD3 has a variety of biological functions. These include stimulatory effects on proliferation, natural killer activity and cytokine production by freshly isolated peripheral T cells. In this study we have characterized anti-GD3 antibody (MoAb Z21) mediated effects on T cell clones. Our data indicate that alpha/beta TCR CD4+ and CD8+ as well as gamma/delta TCR positive T cells can be stimulated resulting in proliferation and cytokine production. This effect could be blocked by cyclosporin A and did not involve the LFA-3 or CD4 molecule. Apart from IFN-gamma and IL-2 production by T helper 1 and T helper 0 cells we have observed production of IL-4 and IL-10 by T helper 2 cells…

In Vitro Expansion of Human Tumor-Reactive CD8+ T Cell Lines Using Superparamagnetic CD3/CD28/CD137 Beads.

2009

Abstract Abstract 5118 Introduction Efficient methods for the reliable in vitro expansion of tumor-reactive T cells will surely broaden the applicability of adoptive T cell therapy in cancer. In this study we investigated the antigen-independent stimulation and expansion of human T cells in peripheral blood mononuclear cells (PBMC) and in long-term cultured tumor-reactive CD8+ T cell lines using superparamagnetic beads coated with antibodies to CD3 and the costimulatory molecules CD28 and CD137. Methods T cell numbers were measured in healthy donor PBMC after in vitro stimulation with Dynabeads® coated with CD3/CD28/CD137 versus Dynabeads® coated with CD3/CD28 (all beads +/- 100 U/mL IL-2) …

PHENOTYPICAL AND FUNCTIONAL ANALYSIS OF HIV SPECIFIC CD4+ AND CD8+ T-CELLS DURING HIV-1 INFECTION: CLINICAL IMPLICATIONS

2012

Delivering all in one: Antigen-nanocapsule loaded with dual adjuvant yields superadditive effects by DC-directed T cell stimulation

2018

Therapeutic vaccination is and remains a major challenge, particularly in cancer treatment. In this process, the effective activation of dendritic cells by a combination of distinctly acting adjuvants and an antigen is crucial for success. While most common vaccine formulations lack the efficiency to trigger sufficient T cell responses in a therapeutic tumor treatment, nanovaccines offer unique properties to tackle that challenge. Here, we report the stepwise development of a nanocapsule for vaccination approaches, comprising a shell consisting of antigen and loaded with a superadditive adjuvant combination. In a first initial step, we identified the combination of resiquimod (R848) and mur…