HIV's Vagina Travelogue

Details of how HIV-1 is transmitted across mucosal barriers remain sparse. In this issue of Immunity, Hladik et al. (2007) describe an organ culture system for imaging HIV-1 interaction with vaginal epithelial T cells and Langerhans cells early after infection

After Hrs with HIV

To efficiently bud off from infected cells, HIV and other enveloped viruses hijack the host cellular machinery that is normally involved in vacuolar protein sorting and multivesicular body (MVB) biogenesis. The HIV Gag protein mimics hepatocyte growth factor–regulated tyrosine kinase substrate (Hrs), a modular adaptor protein that links membrane cargo recognition to its degradation after delivery to MVBs. In contrast to T cells, where HIV budding occurs at the plasma membrane, virus buds into vacuoles of macrophages, a process that may facilitate its spread within the infected host

Plasticity of CD4+ T Cell Lineage Differentiation

The differentiation of naive CD4+ T cells into lineages with distinct effector functions has been considered to be an irreversible event. T helper type 1 (Th1) cells stably express IFN-γ, whereas Th2 cells express IL-4. The discovery and investigation of two other CD4+ T cell subsets, induced regulatory T (iTreg) cells and Th17 cells, has led to a rethinking of the notion that helper T cell subsets represent irreversibly differentiated endpoints. Accumulating evidence suggests that CD4+ T cells, particularly iTreg and Th17 cells, are more plastic than previously appreciated. It appears that expression of Foxp3 by iTreg cells or IL-17 by Th17 cells may not be stable and that there is a great degree of flexibility in their differentiation options. Here, we will discuss recent findings that demonstrate the plasticity of CD4+ T cell differentiation and the biological implications of this flexibility

Itk and Fyn Make Independent Contributions to T Cell Activation

Itk is a member of the Btk/Tec/Itk family of nonreceptor protein tyrosine kinases (PTKs), and has been implicated in T cell antigen receptor (TCR) signal transduction. Lck and Fyn are the Src-family nonreceptor PTKs that are involved in TCR signaling. To address the question of how these members of different families of PTKs functionally contribute to T cell development and to T cell activation, mice deficient for both Itk and either Lck or Fyn were generated. The Itk/Lck doubly deficient mice exhibited a phenotype similar to that of Lck-deficient mice. The phenotype of the Itk/Fyn doubly deficient mice was similar to that of Itk deficient mice. However the Itk/Fyn doubly deficient mice exhibited a more severe defect in TCR-induced proliferation of thymocytes and peripheral T cells than did mice deficient in either kinase alone. These data support the notion that Itk and Fyn both make independent contributions to TCR-induced T cell activation

Multiple Developmental Stage–Specific Enhancers Regulate CD8 Expression in Developing Thymocytes and in Thymus-Independent T Cells

AbstractWe and others have recently identified a CD8 locus enhancer (E8I) that directs expression in mature CD8 single-positive thymocytes and peripheral CD8+ T cells and in extrathymically derived intestinal intraepithelial lymphocytes (IEL). In this study, we show that deletion of E8I by homologous recombination results in reduced CD8αα homodimer expression on IEL. Since CD8 expression on thymus-derived T cells was normal, other enhancers regulate CD8 expression in these cells. By exploiting a transgenic reporter expression assay, we identified three additional enhancers that directed expression in diverse thymocyte subsets and mature T cells but not in CD8αα+ IEL. The results suggest that CD8α expression is primarily regulated by E8I in IEL and by the novel enhancers in the thymus-dependent lineages

Virus-host interactions: new insights from the small RNA world

RNA silencing has a known role in the antiviral responses of plants and insects. Recent evidence, including the finding that the Tat protein of human immunodeficiency virus (HIV) can suppress the host's RNA-silencing pathway and may thus counteract host antiviral RNAs, suggests that RNA-silencing pathways could also have key roles in mammalian virus-host interactions

Severe B Cell Deficiency in Mice Lacking the Tec Kinase Family Members Tec and Btk

The cytoplasmic protein tyrosine kinase Tec has been proposed to have important functions in hematopoiesis and lymphocyte signal transduction. Here we show that Tec-deficient mice developed normally and had no major phenotypic alterations of the immune system. To reveal potential compensatory roles of other Tec kinases such as Bruton's tyrosine kinase (Btk), Tec/Btk double-deficient mice were generated. These mice exhibited a block at the B220+CD43+ stage of B cell development and displayed a severe reduction of peripheral B cell numbers, particularly immunoglobulin (Ig)MloIgDhi B cells. Although Tec/Btknull mice were able to form germinal centers, the response to T cell–dependent antigens was impaired. Thus, Tec and Btk together have an important role both during B cell development and in the generation and/or function of the peripheral B cell pool. The ability of Tec to compensate for Btk may also explain phenotypic differences in X-linked immunodeficiency (xid) mice compared with human X-linked agammaglobulinemia (XLA) patients