Adaptor protein complexes AP-1 and AP-3 are required by the HHV-7 Immunoevasin U21 for rerouting of class I MHC molecules to the lysosomal compartment.

The human herpesvirus-7 (HHV-7) U21 gene product binds to class I major histocompatibility complex (MHC) molecules and reroutes them to a lysosomal compartment. Trafficking of integral membrane proteins to lysosomes is mediated through cytoplasmic sorting signals that recruit heterotetrameric clathrin adaptor protein (AP) complexes, which in turn mediate protein sorting in post-Golgi vesicular transport. Since U21 can mediate rerouting of class I molecules to lysosomes even when lacking its cytoplasmic tail, we hypothesize the existence of a cellular protein that contains the lysosomal sorting information required to escort class I molecules to the lysosomal compartment.

A Thr/Ser dual residue motif in the cytoplasmic tail of human CD1d is important for the down-regulation of antigen presentation following a herpes simplex virus 1 infection.

CD1d-restricted T (natural killer T; NKT) cells are important for controlling herpesvirus infections. Interestingly, herpes simplex virus (HSV) can down-regulate CD1d-mediated activation of NKT cells. We have previously shown that the Thr322 residue in the cytoplasmic tail of human CD1d is important for its intracellular trafficking and functional expression.

Allergic airway disease in mice alters T and B cell responses during an acute respiratory poxvirus infection.

Pulmonary viral infections can exacerbate or trigger the development of allergic airway diseases via multiple mechanisms depending upon the infectious agent. Respiratory vaccinia virus transmission is well established, yet the effects of allergic airway disease on the host response to intra-pulmonary vaccinia virus infection remain poorly defined. As shown here BALB/c mice with preexisting airway disease infected with vaccinia virus developed more severe pulmonary inflammation, higher lung virus titers and greater weight loss compared with mice inoculated with virus alone.

Autonomous murine T-cell progenitor production in the extra-embryonic yolk sac before HSC emergence.

The extra-embryonic yolk sac (YS) is the first hematopoietic site in the mouse embryo and is thought to generate only primitive erythroid and myeloerythroid progenitor cells before definitive HSC emergence within the embryo on E10.5. Here, we have shown the existence of T cell-restricted progenitors in the E9.

Wheezing and itching: The requirement for STAT proteins in allergic inflammation.

The development of allergic inflammation requires the orchestration of gene expression from the inflamed tissue and from the infiltrating immune cells. Since many of the cytokines that promote allergic inflammation signal through hematopoietin family receptors, the Signal Transducer and Activator of Transcription (STAT) family have obligate roles in pro-allergic cytokine-induced gene regulation in multiple cell types. In this review, we summarize work defining the contribution of each of the STAT family members to the development of allergic inflammation, using data from mouse models of allergic inflammation, studies on patient samples and correlations with single nucleotide polymorphisms in STAT genes.

DNA methyltransferase 3a limits the expression of interleukin-13 in T helper 2 cells and allergic airway inflammation.

The inverse correlation between DNA methylation and lineage-specific gene expression during T helper cell development is well documented. However, the specific functions of the de novo methyltransferases Dnmt3a and Dnmt3b in cytokine gene regulation have not been defined. We demonstrate that the expression of Dnmt3a and Dnmt3b are induced to a greater extent in T helper 2 (Th2) cells than in T helper 1 cells during polarization.

STAT3-dependent IL-21 production from T helper cells regulates hematopoietic progenitor cell homeostasis.

The contribution of specific cell types to the production of cytokines that regulate hematopoiesis is still not well defined. We have previously identified T cell-dependent regulation of hematopoietic progenitor cell (HPC) numbers and cycling. In this report, we demonstrated that HPC activity is decreased in mice with STAT3-deficient T cells, a phenotype that is not because of decreased expression of IL-17 or RORγt.

Insight into the mechanism of human herpesvirus 7 U21-mediated diversion of class I MHC molecules to lysosomes.

The U21 open reading frame from human herpesvirus-7 encodes a membrane protein that associates with and redirects class I MHC molecules to the lysosomal compartment. The mechanism by which U21 accomplishes this trafficking excursion is unknown. Here we have examined the contribution of localization, glycosylation, domain structure, and the absence of substrate class I MHC molecules on the ability of U21 to traffic to lysosomes.

Tc17 cells are capable of mediating immunity to vaccinia virus by acquisition of a cytotoxic phenotype.

CD8 T cells can acquire cytokine-secreting phenotypes paralleling cytokine production from Th cells. IL-17-secreting CD8 T cells, termed Tc17 cells, were shown to promote inflammation and mediate immunity to influenza. However, most reports observed a lack of cytotoxic activity by Tc17 cells.

Human herpesvirus 7 u21 downregulates classical and nonclassical class I major histocompatibility complex molecules from the cell surface.

Herpesviruses have evolved numerous strategies to evade detection by the immune system. Notably, most of the herpesviruses interfere with viral antigen presentation to cytotoxic T lymphocytes (CTLs) by removing class I major histocompatibility complex (MHC) molecules from the infected cell surface. Clearly, since the herpesviruses have evolved an extensive array of mechanisms to remove class I MHC molecules from the cell surface, this strategy serves them well.

Human herpesvirus-6A and -6B encode viral immunoevasins that downregulate class I MHC molecules.

Like all other members of the herpesvirus family, the closely related human herpesviruses-6 and -7 (HHV-6,7) persist in their host throughout life. In so doing, without exception, every member of the herpesvirus family has evolved mechanisms to avoid detection by the immune system. In particular, human cytomegalovirus (HCMV), mouse cytomegalovirus (MCMV), human herpesvirus-8 (HHV-8), and herpes simplex virus (HSV) all encode multiple proteins that interfere with proper MHC class I antigen presentation.