Search results for "Cytotoxic"

Interferon-α Abrogates Tolerance Induction by Human Tolerogenic Dendritic Cells

2011

Background Administration of interferon-α (IFN-α) represents an approved adjuvant therapy as reported for malignancies like melanoma and several viral infections. In malignant diseases, tolerance processes are critically involved in tumor progression. In this study, the effect of IFN-α on tolerance induction by human tolerogenic dendritic cells (DC) was analyzed. We focussed on tolerogenic IL-10-modulated DC (IL-10 DC) that are known to induce anergic regulatory T cells (iTregs). Methodology/Principal Findings IFN-α promoted an enhanced maturation of IL-10 DC as demonstrated by upregulation of the differentiation marker CD83 as well as costimulatory molecules. IFN-α treatment resulted in an…

Immune Response to Tumor Stress Proteins—Implications for Vaccine Development Against Cancer

2000

Publisher Summary Stress proteins or heat shock proteins (HSP) belong to the most conserved proteins. The conservation of stress proteins stems from their basic and vital role in cells: Prevention of protein aggregation under stress and physiological conditions. Stress proteins are important target antigens in autoimmune diseases and during certain bacterial infections. This chapter reviews the immunogenicity of stress proteins of tumor cells, stimulation of T cell response by tumor stress proteins and implications this Tcell response have for immunity against the tumor or autoimmunity. The expression of stress proteins in cancer is altered. An overexpression of constitutively expressed or …

Immunodefense in Tunicates: Cells and Molecules

2001

There are several reasons for analyzing tunicate immune systems. First, they can be established as primitive models for understanding fundamental immunological mechanisms by analyzing their individual cells and molecular products either in vivo or in vitro. Discovered mechanisms could provide alternatives to traditional (vertebrate) mammalian (mouse, rat) and emerging models (fish, amphibian reptile) in answering basic questions concerning immunity and disease in protochordates, the ancestors of vertebrates. Second in vitro, biochemical, immunochemical, and serological analyses coupled with molecular approaches are useful as we search for common molecules (e.g. markers of lymphocyte-like ce…

2004

Autoimmune inflammation, such as in rheumatoid arthritis, is characterized by activated Th1 cells without sufficient Th2 differentiation that might downmodulate the chronic immune response. Delineation of the mechanisms that control T-cell differentiation is therefore of major importance for the understanding of the pathogenesis of autoimmune diseases. The transcription factor GATA-3 has been implicated in regulating Th2 cell differentiation in murine T cells in vitro, but its role in vivo and, in particular, in human T-cell differentiation is currently unknown. To dissect the role of GATA-3 in human T-cell differentiation and T-cell-mediated effector functions, we used the unique opportuni…

Dendritic cells and the handling of antigen

2003

Dendritic cells (DC) are a sparsely distributed, migratory group of bone marrow-derived leucocytes that are specialized for the uptake, transport, processing and presentation of antigens to T cells [1,2]. At an immature stage of development DC are considered as the first-line sentinels in immune surveillance of peripheral tissues, including epithelia of the skin and mucosal surfaces, where they sample continuously the antigenic local microenvironment by uptake of self- and exogenous antigen via macropinocytosis/endocytosis [3,4]. The efficiency of DC to initiate an immune response against infectious disease is due to their constant trafficking between peripheral tissues and draining lymph n…

T-T cell collaboration during in vivo responses to antigens coded by the peripheral and central region of the MHC.

1976

MIXED lymphocyte culture (MLC)1 has been used extensively as an in vitro model to analyse the reactivity of T cells to antigens coded by the major histocompatibility complex (MHC). When murine T responder cells are exposed in vitro to allogeneic lymphoid cells (stimulator cells) they proliferate and cytotoxic T lymphocytes (CTL) are generated2,3. Antigens coded by the central I region of the MHC are chiefly responsible for triggering proliferation4,5, whereas the target antigen of the CTL generated is either a H–2K or H–2D region or a I–A subregion gene product5–8. This dichotomy in the antigenic requirement of a MLC seems to be reflected at the level of the responding T lymphocytes. Two di…

Tuning tumor-specific T-cell activation: a matter of costimulation?

2002

Abstract The stimulation of a specific antitumor immune response, involving the recruitment of T cells and induction of T-cell effector functions, is an attractive possibility for cancer immunotherapy. In the past few years, advances in our understanding of the mechanisms of T-cell activation and costimulation have provided the basis for strategies to enhance antitumor immunity and break tolerance. These strategies include the equipment of tumor cells with costimulatory molecules such as B7, blockade of inhibitory signals on T cells (e.g. through cytotoxic T-lymphocyte antigen 4) and grafting of T cells with antigen-triggered, recombinant costimulatory receptors. Combining antigen-triggered…

Identification and Functional Characterization of Human Cd4+Cd25+ T Cells with Regulatory Properties Isolated from Peripheral Blood

2001

A subpopulation of peripheral human CD4(+)CD25(+) T cells that expresses CD45RO, histocompatibility leukocyte antigen DR, and intracellular cytotoxic T lymphocyte-associated antigen (CTLA) 4 does not expand after stimulation and markedly suppresses the expansion of conventional T cells in a contact-dependent manner. After activation, CD4(+)CD25(+) T cells express CTLA-4 on the surface detectable for several weeks. These cells show a G1/G0 cell cycle arrest and no production of interleukin (IL)-2, IL-4, or interferon (IFN)-gamma on either protein or mRNA levels. The anergic state of CD4(+)CD25(+) T cells is not reversible by the addition of anti-CD28, anti-CTLA-4, anti-transforming growth fa…

Human CD4+CD25+ T cells derived from the majority of atopic donors are able to suppress TH1 and TH2 cytokine production

2003

Abstract Background: Recently, it has been established that CD4 + CD25 + T cells with regulatory capacity are present in human peripheral blood, inhibiting allogeneic proliferation and cytokine production of preactivated CD4 + CD25 − respond-er T cells. Objective: The aim of this study was to analyze in an allergen-specific setting whether such regulatory CD4 + CD25 + T cells also exist and function normally in atopic individuals, especially concerning the inhibition of T H 2 cytokines. Methods: For this purpose, CD4 + CD25 − or CD4 + CD25 + T cells from donors allergic to grass or birch pollen (mainly with rhinitis) or from healthy nonatopic donors were stimulated in the presence of autolo…

SARS-CoV-2 in patients with cancer: possible role of mimicry of human molecules by viral proteins and the resulting anti-cancer immunity

2021

AbstractA few reports suggest that molecular mimicry can have a role in determining the more severe and deadly forms of COVID-19, inducing endothelial damage, disseminated intravascular coagulation, and multiorgan failure. Heat shock proteins/molecular chaperones can be involved in these molecular mimicry phenomena. However, tumor cells can display on their surface heat shock proteins/molecular chaperones that are mimicked by SARS-CoV-2 molecules (including the Spike protein), similarly to what happens in other bacterial or viral infections. Since molecular mimicry between SARS-CoV-2 and tumoral proteins can elicit an immune reaction in which antibodies or cytotoxic cells produced against t…