Recent studies have detected Wilms tumor antigen (WT1)-specific cytotoxic T lymphocytes (CTLs) in patients with acute myelogenous leukemia (AML) and chronic myelogenous leukemia (CML) and demonstrated that most of these CTLs were low avidity. Although HLA-mismatched donors can mount high-avidity CTLs against HLA-A2-presented peptides of WT1, a dominant anti-alloimmune response usually obscures ...

Both CD4+ T cells and macrophages are major reservoirs of HIV-1. Previous study showed that HIV-1-specific cytolytic T lymphocytes (CTLs) hardly recognize HIV-1-infected CD4+ T cells because of Nef-mediated HLA class I down-regulation, suggesting that HIV-1 escapes from HIV-1-specific CTLs and continues to replicate in HIV-1-infected donors. On the other hand, the CTL recognition of HIV-1-infec...

PURPOSE Carbonic anhydrase 9 (CA9) is the most promising molecular marker described for renal cell carcinoma (RCC) to date. We investigated whether transduction of monocytes from peripheral blood with adenovirus encoding the CA9 gene (AdV-CA9) could stimulate a T-cell mediated immune response against cancer cells expressing CA9. The ability to consistently generate a T-cell response is an impor...

Although the immune system evolved to fight infections, it may also attack and destroy solid tumors. In most cases, tumor rejection is initiated by CD8(+) cytotoxic T lymphocytes (CTLs), which infiltrate solid tumors, recognize tumor antigens, and kill tumor cells. We use a combination of two-photon intravital microscopy and immunofluorescence on ordered sequential sections to analyze the infil...

The antitumor effect of adoptively transferred tumor-specific cytotoxic T lymphocytes (CTLs) is impaired by the limited capacity of these cells to expand within the tumor microenvironment. Administration of interleukin 2 (IL-2) has been used to overcome this limitation, but the systemic toxicity and the expansion of unwanted cells, including regulatory T cells, limit the clinical value of this ...

Using granzyme B-deficient mice obtained by gene targeting, we previously demonstrated that granzyme B is required for the rapid induction of apoptotic target cell death by cytotoxic T lymphocytes (CTLs); however, CTLs are also equipped with additional effector mechanisms. In the present study, we examined the mechanisms responsible for granzyme B-independent cytotoxicity using in vitro lytic a...

LFA-1 mediates binding of cytotoxic T lymphocytes (CTLs) to target cells. However, the role of LFA-1 in CTLs beyond its cell adhesion function has been unclear. We have investigated the role of LFA-1 in reorganization of the actin cytoskeleton, an essential step in cell-mediated cytotoxicity. Binding of LFA-1 to ICAM-1, but not anti-LFA-1 cross-linking, induces the accumulation of talin, WASP a...

Hepatitis B virus core antigen (HBcAg) is thought to be a major target for specific cytotoxic T cells (CTLs) in hepatitis B virus infections. A single dose of hepatitis C virus nonstructural 3/4A DNA (<5 microg) effectively primes functional specific CTLs, independently of CD4(+) T helper cells and by different routes of immunization. In contrast, HBcAg-specific CTL priming was T helper cell de...

Reports from a number of laboratories have shown that mAbs against the T3-Ti receptor complex cause an increase in cytosolic-free Ca2+ [( Ca2+]i) and the hydrolysis of phosphatidylinositolbisphosphate (PIP2) in CTLs. In the present report we show that activation of CTLs by their specific targets causes: (a) release of Ca2+ from intracellular stores; (b) transient formation of inositol trisphosp...

Priming of cytotoxic T lymphocytes (CTLs) by dendritic cells (DCs) is crucial for elimination of pathogens and malignant cells. To activate CTLs, DCs present antigenic peptide-complexed MHC class I molecules (MHC-I) that will be recognized by the CTLs with T cell receptors and CD8 molecules. Here we show that paired Ig-like receptor (PIR)-B, an MHC-I receptor expressed on antigen-presenting cel...