Midline 1 (MID1) is a microtubule-associated ubiquitin ligase that regulates protein phosphatase 2A activity. Loss-of-function mutations in MID1 lead to the X-linked Opitz G/BBB syndrome characterized by defective midline development during embryogenesis. Here, we show that MID1 is strongly upregulated in murine cytotoxic lymphocytes (CTLs), and that it controls TCR signaling, centrosome traffi...

Although cytotoxic T lymphocytes (CTLs) are thought to be involved in the control of human immunodeficiency virus-type 1 (HIV-1) infection, it has not been possible to demonstrate a direct relation between CTL activity and plasma RNA viral load. Human leukocyte antigen-peptide tetrameric complexes offer a specific means to directly quantitate circulating CTLs ex vivo. With the use of the tetram...

The antiviral role of CD8+ cytotoxic T lymphocytes (CTLs) in human immunodeficiency virus type 1 (HIV-1) infection is poorly understood. Specifically, the degree to which CTLs reduce viral replication by killing HIV-1-infected cells in vivo is not known. Here we employ mathematical models of the infection process and CTL action to estimate the rate that CTLs can kill HIV-1-infected cells from i...

It is believed that Nef-mediated HLA class I down-regulation is one of the mechanisms that allow HIV-1-infected cells to escape from being killed by HIV-1-specific human CTLs. In this study, we show that the effect of Nef-mediated HLA class I down-regulation on the ability of HIV-1-specific CTLs to suppress HIV-1 replication is epitope dependent. The CTLs specific for two Pol epitopes presented...

Cytotoxic T lymphocyte (CTL)-induced death triggered by the granule exocytosis pathway involves the perforin-dependent delivery of granzymes to the target cell. Gene targeting has shown that perforin is essential for this process; however, CTL deficient in the key granzymes A and B maintain the ability to kill their targets by granule exocytosis. It is not clear how granzyme AB(-/-) CTLs kill t...

Recent advances have made haploidentical transplantation for leukemia feasible, but the rigorous T-cell depletion used contributes to the high relapse rates observed. We have attempted to improve the graft-versus-leukemia (GVL) effect by generating allorestricted cytotoxic T lymphocytes (CTLs) directed against human CD45. Such CTLs should recognize patient hematopoietic cells including leukemia...

Abstract BACKGROUND Although immunotherapy holds promise for producing durable outcomes in GBM, a major obstacle is the limited ability of cytotoxic T lymphocytes (CTLs) to home tumor. CTLs are recruited via long-range signaling mediated by diffusion chemokines present inflammatory environments. During glioma formation, tumors manufacture immune-suppressive and cytokines that co-opt resident ce...

Abstract In a context where the criminal courts have been drastically affected by coronavirus, this paper seeks to demonstrate that presumption of innocence risks becoming further casualty Covid-19. It will argue prolonged pre-trial detention unconvicted defendants has sanctioned senior judiciary under Custody Time Limit (CTL) Regulations. Following series important CTL decisions, universal pos...

During the pre-erythrocytic asymptomatic phase of malarial infection, sporozoites develop transiently inside less than 100 hepatocytes that subsequently release thousands of merozoites. Killing of these hepatocytes by cytotoxic T cells (CTLs) confers protection to subsequent malarial infection, suggesting that this bottleneck phase in the parasite life cycle can be targeted by vaccination. Duri...

Although the cytotoxic mechanisms of murine CTLs have been investigated extensively using various mutant and knockout mice, those of human CTLs, especially CD4+ CTLs, are still obscure. To clarify the roles of perforin in Ag-specific cytotoxicity mediated by human CD4+ CTLs, alloantigen-specific and HSV-specific human CD4+ T lymphocyte bulk lines and clones were established from a patient with ...