Cytotoxic T cell

About: Cytotoxic T cell is a research topic. Over the lifetime, 92492 publications have been published within this topic receiving 4768477 citations. The topic is also known as: killer T cell & cytotoxic T lymphocyte.

Persistence of Memory CD8 T Cells in MHC Class I-Deficient Mice

Abstract: An understanding of how T cell memory is maintained is crucial for the rational design of vaccines. Memory T cells were shown to persist indefinitely in major histocompatibility complex (MHC) class I-deficient mice and retained the ability to make rapid cytokine responses upon reencounter with antigen. In addition, memory CD8 T cells, unlike naive cells, divided without MHC-T cell receptor interactions. This "homeostatic" proliferation is likely to be important in maintaining memory T cell numbers in the periphery. Thus, after naive CD8 T cells differentiate into memory cells, they evolve an MHC class I-independent "life-style" and do not require further stimulation with specific or cross-reactive antigen for their maintenance.

Increase of Regulatory T Cells in the Peripheral Blood of Cancer Patients 1

Abstract: Purpose: T cells constitutively expressing both CD4 and CD25 are essential for maintenance of self-tolerance and therefore have been referred to as regulatory T cells (Treg). Experimental tumor models in mice revealed that Tregs are potent inhibitors of an antitumor immune response. The current study was designed to determine whether cancer patients exhibit an expanded Treg pool. Experimental Design: The frequency of Tregs in the peripheral blood of 42 patients suffering from epithelial malignancies and from 34 healthy controls was determined by flow cytometry. The immunoregulatory properties of CD4CD25 and CD4CD25 T cells were characterized by proliferation and suppression assays. Cocultures with natural killer (NK) cells were performed to determine the impact of Tregs on NK-mediated cytotoxicity. Results: Patients with epithelial malignancies show an increase of CD4CD25 T cells in the peripheral blood with characteristics of Tregs, i.e., they are CD45RA, CTLA-4, and transforming growth factor . Notably, CD4 T cells from cancer patients are characterized by an impaired proliferative capacity, which is restored to the extend of CD25depleted CD4 T cells from control persons by prior removal of CD25 T cells. In contrast to CD4CD25 T cells, isolated CD4CD25 T cells from cancer patients were anergic towards T cell receptor stimulation. In addition, CD4CD25 T cells suppressed the proliferation of CD4CD25 T cells. When cultured together with CD56 NK-cells, CD4CD25 T cells from cancer patients effectively inhibited NK-cell-mediated cytotoxicity. Conclusions: Thus, we provide evidence of an increased pool of CD4CD25 regulatory T cells in the peripheral blood of cancer patients with potent immunosuppressive features. These findings should be considered for the design of immunomodulatory therapies such as dendritic cell vaccination.

VEGF-A modulates expression of inhibitory checkpoints on CD8+ T cells in tumors.

Abstract: Immune escape is a prerequisite for tumor development. To avoid the immune system, tumors develop different mechanisms, including T cell exhaustion, which is characterized by expression of immune inhibitory receptors, such as PD-1, CTLA-4, Tim-3, and a progressive loss of function. The recent development of therapies targeting PD-1 and CTLA-4 have raised great interest since they induced long-lasting objective responses in patients suffering from advanced metastatic tumors. However, the regulation of PD-1 expression, and thereby of exhaustion, is unclear. VEGF-A, a proangiogenic molecule produced by the tumors, plays a key role in the development of an immunosuppressive microenvironment. We report in the present work that VEGF-A produced in the tumor microenvironment enhances expression of PD-1 and other inhibitory checkpoints involved in CD8+ T cell exhaustion, which could be reverted by anti-angiogenic agents targeting VEGF-A–VEGFR. In view of these results, association of anti-angiogenic molecules with immunomodulators of inhibitory checkpoints may be of particular interest in VEGF-A-producing tumors.

A dominant function for interleukin 27 in generating interleukin 10–producing anti-inflammatory T cells

Abstract: Regulatory T cells (Treg cells) expressing the transcription factor Foxp3 are key in maintaining the balance of immune homeostasis. However, distinct induced T regulatory type 1 (Tr1) cells that lack Foxp3 expression also regulate T cell function, mainly by producing the immunosuppressive cytokine interleukin 10 (IL-10). However, the factors required for the induction of IL-10-producing suppressive T cells are not fully understood. Here we demonstrate that dendritic cells modified by Treg cells induced the generation of IL-10-producing Tr1 cells. The differentiation of naive CD4+ T cells into IL-10-producing cells was mediated by IL-27 produced by the Treg cell–modified dendritic cells, and transforming growth factor-β amplified the generation of induced IL-10+ Tr1 cells by IL-27. Thus, IL-27 and transforming growth factor-β promote the generation of IL-10-producing Tr1 cells.