The functions of type I and type II natural killer T cells in inflammatory bowel diseases.

CD1d-restricted natural killer T (NKT) cells are a distinct subset of T cells that rapidly produce an array of cytokines on activation and play a critical role in regulating various immune responses. NKT cells are classified into 2 groups based on differences in T-cell receptor usage. Type I NKT cells have an invariant T-cell receptor α-chain and are readily detectable by α-galactosylceramide (α-GalCer)-loaded CD1d tetramers.

dysregulation of CD1d-restricted type ii natural killer T cells leads to spontaneous development of colitis in mice.

Background & Aims: CD1d-restricted natural killer (NK) T cells are a subset of immunoregulatory T cells that comprise type I (express the semi-invariant T-cell receptor [TCR] and can be detected using the α-galactosylceramide/CD1d tetramer) and type II (express diverse TCRs and cannot be directly identified). Studies in mouse models of inflammatory bowel disease revealed a complex role for type I NKT cells in the development of colitis. Type II NKT cells have been associated with intestinal inflammation in patients with ulcerative colitis.

CD1-restricted adaptive immune responses to Mycobacteria in human group 1 CD1 transgenic mice.

Group 1 CD1 (CD1a, CD1b, and CD1c)-restricted T cells recognize mycobacterial lipid antigens and are found at higher frequencies in Mycobacterium tuberculosis (Mtb)-infected individuals. However, their role and dynamics during infection remain unknown because of the lack of a suitable small animal model. We have generated human group 1 CD1 transgenic (hCD1Tg) mice that express all three human group 1 CD1 isoforms and support the development of group 1 CD1-restricted T cells with diverse T cell receptor usage.

Polymorphisms in CD1d affect antigen presentation and the activation of CD1d-restricted T cells.

CD1 proteins constitute a distinct lineage of antigen-presenting molecules specialized for the presentation of lipid antigens to T cells. In contrast to the extensive sequence polymorphism characteristic of classical MHC molecules, CD1 proteins exhibit limited sequence diversity. Here, we describe the identification and characterization of CD1d alleles in wild-derived mouse strains.

A cell-type specific CD1d expression program modulates invariant NKT cell development and function.

Invariant NK T (iNKT) cells are a distinct subset of T cells that rapidly produce an array of immunoregulatory cytokines upon activation. Cytokines produced by iNKT cells subsequently transactivate other leukocytes and elicit their respective effector functions. In this way, iNKT cells play a central role in coordinating the development of immune responses in a variety of settings.

Selective inhibition of anthrax edema factor by adefovir, a drug for chronic hepatitis B virus infection.

Edema factor (EF), a key virulence factor in anthrax pathogenesis, has calmodulin (CaM)-activated adenylyl cyclase activity. We have found that adefovir dipivoxil, a drug approved to treat chronic infection of hepatitis B virus, effectively inhibits EF-induced cAMP accumulation and changes in cytokine production in mouse primary macrophages. Adefovir diphosphate (PMEApp), the active cellular metabolite of adefovir dipivoxil, inhibits the adenylyl cyclase activity of EF in vitro with high affinity (K(i) = 27 nM).

A role for class A scavenger receptor in dendritic cell nibbling from live cells.

Monocyte-derived dendritic cells (DC) possess the unique capacity to capture Ag from live cells through intimate cell contact, a process referred to as nibbling. We sought to define the receptor(s) mediating DC nibbling. Uptake of fluorescently labeled plasma membrane from live cells by DC was inhibited by protease treatment and by a panel of polyanionic ligands, implicating scavenger receptors (SR) in this process.

Disrupted homeostasis of Langerhans cells and interdigitating dendritic cells in monkeys with AIDS.

Langerhans cells (LCs) are immature dendritic cells (DCs) that capture antigen in peripheral tissues and migrate to draining lymph nodes, where they reside in the paracortex as interdigitating dendritic cells (IDCs). We studied the effects of simian immunodeficiency virus (SIV) on LCs and IDCs during different stages of infection in monkeys. LCs isolated from monkeys with acute SIV infection or acquired immunodeficiency syndrome (AIDS) underwent normal maturation in vitro, including a switch in chemokine receptor expression from CCR5 to CXCR4 and CCR7.