Fuc-TVII is required for T helper 1 and T cytotoxic 1 lymphocyte selectin ligand expression and recruitment in inflammation, and together with Fuc-TIV regulates naive T cell trafficking to lymph nodes.

To determine how the alpha(1,3)fucosyltransferases Fuc-TIV and Fuc-TVII, and the selectin ligands they control may contribute to the adaptive immune response, contact hypersensitivity (CHS) was characterized in mice deficient in either or both enzymes. We find a substantial CHS deficiency in Fuc-TVII(-/-) mice, and a complete deficiency in Fuc-TIV(-/-)/Fuc-TVII(-/-) mice. These defects are not accounted for by alterations in the number or function of epidermal Langerhans cells required for cutaneous antigen processing and presentation. By contrast, defective CHS in Fuc-TVII(-/-) mice or Fuc-TIV(-/-)/Fuc-TVII(-/-) mice is attributed in part to prominent, or nearly complete deficiencies, respectively, in the complement of naive T lymphocytes available in lymph nodes for antigen-dependent activation, expansion, differentiation, and dissemination. Fuc-TVII deficiency also deletes expression of E- and P-selectin ligands by Th1 and T cytotoxic 1 (Tc1) lymphocytes, annuls T cell trafficking to inflamed cutaneous sites in vivo, and thereby controls an essential component of the efferent phase of the cutaneous immune response. These observations indicate that collaborative contributions of Fuc-TIV and Fuc-TVII to L-selectin ligand synthesis, and to lymphocyte recruitment, are requisite components of the primary cellular immune response, and assign an essential role to Fuc-TVII in control of E- and P-selectin ligand expression by Th1 and Tc1 lymphocytes.

Altered membrane trafficking in activated bone marrow-derived macrophages.

Activation of macrophages with interferon-gamma (IFN-gamma) and lipopolysaccharide (LPS) leads to increased intracellular resistance to microbes and increased major histocompatibility complex class II-restricted antigen presentation, processes that both use the vacuolar compartment. Despite the requirement of the macrophage vacuolar compartment for microbicidal activities and antigen processing, the rates of endocytosis and membrane trafficking in activated macrophages are not clearly defined. In this study, vacuolar compartment dynamics were analyzed in murine bone marrow-derived macrophages activated with LPS and/or IFN-gamma, conditions that increased macrophage nitric oxide production and resistance to infection by Listeria monocytogenes. Relative to nonactivated cells, activated macrophages showed diminished rates of fluid-phase pinocytosis and phagocytosis and delayed progression of macropinosomes and phagosomes to late endosomes and lysosomes. In contrast to the slowing of membrane trafficking, rates of macropinosome acidification were similar between activated and nonactivated cells. One consequence of this slowed membrane trafficking in activated macrophages was a prolonged exposure of incoming molecules to an acidic nonlysosomal compartment, a condition which may facilitate microbicidal chemistries or antigen processing.

Cognitive, psychosocial, and physical development in infants and children with end-stage renal disease.

The purpose of this article is to synthesize research related to the cognitive, physical, and psychosocial development of children with end-stage renal disease who are receiving conservative management, hemodialysis or peritoneal dialysis, or who have received transplants. An impressive array of research in these three areas of development was found, but more work is needed. Suggestions are made for more multicenter research with larger sample sizes and greater generalizability. In addition, more developmental research that includes measures of renal disease, such as age at onset, severity of disease, and length of time in renal failure, is needed.